Compositions and methods relating to carboxylic acid ionic liquids

Abstract

The technology described herein is directed to ionic liquids and methods of drug delivery.

Description

COMPOSITIONS AND METHODS RELATING TO CARBOXYLIC ACID IONIC LIQUIDSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit under 35 U.S.C. § 119 of U.S. Provisional Application No. 63 / 707,787 filed October 16, 2024, U.S. Provisional Application No. 63 / 682,426 filed August 13, 2024, U.S. Provisional Application No. 63 / 678,882 filed August 2, 2024, and U.S. Provisional Application No. 63 / 678,772 filed August 2, 2024, the contents of which are incorporated herein by reference in their entireties.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on July 14, 2025, is named 002806-000149WOPT_SL.txt and is 19,251 bytes in size.TECHNICAL FIELD

[0003] The technology described herein relates to ionic liquids for stabilization and deliver}' of active compounds.BACKGROUND

[0004] Monoclonal antibodies (mAbs) are the single largest class of therapeutics used in various indications including oncology, immunology, and neurology. However, antibodies are usually administered intravenously, which increases costs and reduces availability of such treatments.

[0005] The ability to effectively administer antibodies by subcutaneous injection would be highly beneficial. But to administer subcutaneously, it is necessary to provide formulations with high concentrations, low viscosities, and high shelf-stability. Existing strategies have not yet accomplished this goal are limited either by low mAb concentrations or high concentrations of other elements of the formulations.SUMMARY

[0006] The inventors have now identified several ionic liquids that allow the preparation of ultra- high concentration antibody formulations while keeping the amount of ionic liquid low and allowing for an injectable level of viscosity. Such compositions pennit efficacious subcutaneous delivery of antibody therapies for a wide range of conditions.

[0007] In one aspect of any of the embodiments, described herein is a composition comprising at least one ionic liquid comprising: an anion which is selected from the group consisting of: hexenoic acid, pentenoic acid, hexanoic acid, methylpentenoic acid, butyric acid, heptanoic acid, dimethylacrylic acid (DMAA); lactic acid; glycolic acid; gluconic acid; glutaric acid; tartaric acid; citric acid; and EDTA; a cation which is a quaternary ammonium.

[0008] In some embodiments of any of the aspects, the anion is selected from the group consisting of: hexenoic acid, hexanoic acid, methylpentenoic acid, and heptanoic acid. In some embodiments of any of the aspects, the anion is selected from the group consisting of: hexanoic acid, methy lpentenoic acid, and heptanoic acid.

[0009] In some embodiments of any of the aspects, the cation is choline or acetylcholine.

[0010] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid;Choline methylpentenoic acid;Choline hexenoic acid;Acetylcholine hexanoic acid; andMethacholine hexenoic acid.

[0011] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1:1;Choline heptanoic acid at a catiomanion ratio of 2: 1;Choline methylpentenoic acid at a catiomanion ratio of 1 :2;Choline hexenoic acid at a catiomanion ratio of 1 :2;Acetylcholine hexanoic acid at a cation: anion ratio of 1 : 1 ; and Methacholine hexenoic acid at a cation: anion ratio of 1 : 1.

[0012] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid;Choline methy lpentenoic acid;Choline hexenoic acid; and Acetylcholine hexanoic acid.

[0013] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a catiomanion ratio of 2: 1 ;Choline methylpentenoic acid at a catiomanion ratio of 1:2;Choline hexenoic acid at a catiomanion ratio of 1 :2; and Acetylcholine hexanoic acid at a cation: anion ratio of 1 : 1.

[0014] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid; andCholine methylpentenoic acid.

[0015] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a catiomanion ratio of 2:1; andCholine methylpentenoic acid at a catiomanion ratio of 1:2.

[0016] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid;Choline methylpentenoic acid;Choline hexenoic acid; andMethacholine hexenoic acid.

[0017] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a catiomanion ratio of 2:1;Choline methylpentenoic acid at a catiomanion ratio of 1:2;Choline hexenoic acid at a catiomanion ratio of 1 :2; andMethacholine hexenoic acid at a cation: anion ratio of 1 : 1.

[0018] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline methylpentenoic acid; andCholine hexenoic acid.

[0019] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline methylpentenoic acid at a catiomanion ratio of 1:2: andCholine hexenoic acid at a catiomanion ratio of 1 :2.

[0020] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline methylpentenoic acid; andCholine hcxcnoic acid.

[0021] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline methylpentenoic acid at a catiomanion ratio of 1:2: and Choline hexenoic acid at a catiomanion ratio of 1 :2.

[0022] In some embodiments of any of the aspects, the ionic liquid is Choline hexanoic acid. In some embodiments of any of the aspects, the ionic liquid is Choline heptanoic acid. In some embodiments of any of the aspects, the ionic liquid is Choline methylpentenoic acid. In some embodiments of any of the aspects, the ionic liquid is Choline hexenoic acid. In some embodiments of any of the aspects, the ionic liquid is Acetylcholine hexanoic acid. In some embodiments of any of the aspects, the ionic liquid is Methacholine hexenoic acid.

[0023] In some embodiments of any of the aspects, the ionic liquid is Choline hexanoic acid at a cation: anion ratio of 1:1. In some embodiments of any of the aspects, the ionic liquid is Choline heptanoic acid at a catiomanion ratio of 2: 1. In some embodiments of any of the aspects, the ionic liquid is Choline methylpentenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the ionic liquid is Choline hexenoic acid at a catiomanion ratio of 1 :2. In some embodiments of any of the aspects, the ionic liquid is Acetylcholine hexanoic acid at a catiomanion ratio of 1:1. In some embodiments of any of the aspects, the ionic liquid is Methacholine hexenoic acid at a cation: anion ratio of 1 : 1.

[0024] In some embodiments of any of the aspects, the anion is selected from the group consisting of: lactic acid; glycolic acid; gluconic acid; glutaric acid; tartaric acid; citric acid; and EDTA. In some embodiments of any of the aspects, the anion is selected from the group consisting of: glutaric acid and EDTA.

[0025] In some embodiments of any of the aspects, the quaternary ammonium comprises an ester group. In some embodiments of any of the aspects, the cation is choline, acety lcholine, or methacholine. In some embodiments of any of the aspects, the cation is choline.

[0026] In some embodiments of any of the aspects, the ionic liquid comprises a ratio of cation to anion of from about 2: 1 to about 1:2. In some embodiments of any of the aspects, the ionic liquid comprises a ratio of cation to anion of from about 2: 1 to about 1 : 1. In some embodiments of any of the aspects, the ionic liquid comprises a ratio of cation to anion of about 2:1. In some embodiments of any of the aspects, the ionic liquid comprises a ratio of cation to anion of about 1 : 1. In some embodiments of any of the aspects, the ionic liquid has a catiomanion ratio of less than 1 : 1. In some embodiments of any of the aspects, the ionic liquid has a catiomanion ratio with an excess of cation.

[0027] In some embodiments of any of the aspects, the composition further comprises at least a second ionic liquid. In some embodiments of any of the aspects, the at least one ionic liquid and the second ionic liquid each comprise a different anion.

[0028] In some embodiments of any of the aspects, the composition further comprises at least one active compound in combination with the at least one ionic liquid. In some embodiments of any of the aspects, the active compound is present at a concentration of at least 100 tng / mL. In some embodiments of any of the aspects, the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the active compound is present at a concentration of at least 300 mg / mL. In some embodiments of any of the aspects, the active compound comprises a polypeptide. In some embodiments of any of the aspects, the polypeptide is an antibody or antibody reagent. In some embodiments of any of the aspects, the active compound has a molecular weight of greater than 450. In some embodiments of any of the aspects, the active compound has a molecular weight of greater than 500.

[0029] In some embodiments of any of the aspects, the ionic liquid is at a concentration of from about 1 to about 10%v / v. In some embodiments of any of the aspects, the ionic liquid is at a concentration of at least l%v / v. In some embodiments of any of the aspects, the ionic liquid is at a concentration of less than 20%v / v. In some embodiments of any of the aspects, the ionic liquid is at a concentration of less than 10%v / v. In some embodiments of any of the aspects, the ionic liquid is at a concentration of from about 1 to about 5%v / v.

[0030] In some embodiments of any of the aspects, the ionic liquid is at a concentration of at least 0.1%w / v. In some embodiments of any of the aspects, the ionic liquid is at a concentration of from about 10 to about 70%w / v. In some embodiments of any of the aspects, the ionic liquid is at a concentration of from about 30 to about 50%w / v. In some embodiments of any of the aspects, the ionic liquid is at a concentration of from about 30 to about 40%w / v. In some embodiments of any of the aspects, the ionic liquid is at a concentration of less than 10%w7v. In some embodiments of any of the aspects, the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the composition has a viscosity of 1 cP to 20 cP.

[0031] In some embodiments of any of the aspects, the composition is formulated for administration transdennally subcutaneously, intradermally, or parenterally . In some embodiments of any of the aspects, the composition is formulated for subcutaneous administration. In some embodiments of any of the aspects, the composition is formulated for transdermal administration.

[0032] In some embodiments of any of the aspects, the composition further comprises at least one non-ionic surfactant. In some embodiments of any of the aspects, the composition further comprises a pharmaceutically acceptable carrier.

[0033] In some embodiments of any of the aspects, the composition is an admixture. In some embodiments of any of the aspects, the composition is provided in one or more nanoparticles. In some embodiments of any of the aspects, the composition comprises one or more nanoparticles comprising the active compound, the nanoparticles in solution or suspension in a composition comprising the ionic liquid.

[0034] In one aspect of any of the embodiments, described herein is a method of administering at least one active compound to a subject, the method comprising administering a composition described herein. In some embodiments of any of the aspects, the composition is administered once In some embodiments of any of the aspects, the composition is administered in multiple doses. In some embodiments of any of the aspects, the administering is transdermally, subcutaneously, intradermally, or parenterally. In some embodiments of any of the aspects, the administering is subcutaneous.

[0035] In one aspect of any of the embodiments, described herein is a composition described herein for use in a method of administering at least one active compound to a subject.

[0036] In one aspect of any of the embodiments, described herein is a composition described herein for use in a method of stabilizing at least one active compound.

[0037] In one aspect of any of the embodiments, described herein is a composition described herein for use in a method of solubilizing at least one active compound.

[0038] In one aspect of any of the embodiments, described herein is a composition described herein for use in a method of increasing the bioavailability7of at least one active compound.

[0039] In one aspect of any of the embodiments, described herein is a composition described herien for use in a method of providing a high concentration formulation of at least one active compound.

[0040] In one aspect of any of the embodiments, described herein is a composition described herein for use in a method of providing a high concentration, injectable viscosity7formulation of at least one active compound.

[0041] In some embodiments of any of the aspects, the composition is administered once. In some embodiments of any of the aspects, the composition is administered in multiple doses. In some embodiments of any of the aspects, the administering is transdermally, subcutaneously, intradermally, or parenterally. In some embodiments of any of the aspects, the administering is subcutaneous.BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Fig.l depicts a graph showing that antibody (36%) dominates clinically administered protein therapeutics, of which 34% are administered subcutaneously.

[0043] Fig. 2 depicts a schematic of DES-antibody non-specific interactions (hydrophobic, electrostatic, hydrogen bonding) in bulk phase.

[0044] Fig. 3 depicts the library of cations and anions employed in initial DES library synthesis. LogP was used as a metric of hydrophobicity.

[0045] Fig. 4 depicts the rheological properties of 10% (v / v) DES formulated with 100 mg / mL polyclonal human IgG (n=5). Dotted horizontal line equates to 25 cP cutoff for subcutaneous injection. Data plotted as mean + standard error (SEM).

[0046] Figs. 5A-5N depict antibody structure analysis via circular dichroism for DES-IgG samples exposed to room temperature, cold (4C), and hot (37C) storage conditions under constant rotation (n=3). Average particle radius (Rli) for formulations was quantified via dynamic light scattering with error represented as standard error (SEM). AA = auto-attenuation.

[0047] Fig. 6 depicts a graph of antibody functional assessment via ELISA for DES-IgG formulations exposed to room temperature, cold (4°C), and hot (37°C) storage conditions under constant rotation (n=3). Data was normalized to saline control.

[0048] Figs. 7A-7M: 6-day biodistribution kinetics for screened DES-IgG formulations at 10% DES and 100 mg / mL mouse IgG. (top, left) Mice (n=5) were injected subcutaneously with a mixture of unmodified and tagged IgG (9.5 :0.5), with collected serum extrapolated to a concertation value using a standard curve, (bottom right) Serum AUC p-values and average fluorescent intensity values at the injection site collected via IVIS used in candidates for further experimentation.

[0049] Figs. 8A-8E depict 21-day biodistribution kinetics for screened DES-IgG formulations at 10% DES and 100 mg / mL mouse IgG. Mice (n=8) were injected subcutaneously with a mixture of unmodified and tagged IgG (9.3:0.7) and analyzed as done previously. Bioavialability is calculated via AUC measurements as a percentage of IgG administered intravenously (I.V.).

[0050] Figs. 9A-9B. Fig. 9A depicts rheological data for DES formulated with 300 mg / mL human IgG at a range of concentrations. Fig. 9B depicts 6-day biodistribution kinetics for screened DES-IgG formulations at 10% DES and 300 mg / mL mouse IgG. Mice (n=5) were injected subcutaneously with a mixture of unmodified and tagged IgG (9.5:0.5) and analyzed as done previously.

[0051] Fig. 10 demostrates extrapolating DES-IgG viscosity measurements (curve marked (1)) via protein-free conductivity measurements (curve marked (2)). Mathematical model (curve marked (3)) was derived from a library of candidate DES-IgG formulations.

[0052] Fig. 11 depicts carboxylic acid based ionic liquid library.

[0053] Figs. 12A-12E depict 21 biodistribution kinetics in an animal trial of 100 mg / mL antibody formulations.

[0054] Figs. 13A-13E depict rheology of 300 mg / mL antibody fonnulations.

[0055] Figs. 14A-14G depict 6 biodistribution kinetics in an animal trial of 300 mg / mL antibody formulations.

[0056] Fig. 15 depict electrostatic elucidation proceses.

[0057] Fig. 16 depict in vivo bioavailability proceses.

[0058] Fig. 17 depicts viscosity of 100 mg / mL antibody formulations.

[0059] Fig. 18 depicts in vivo pharmacokinetics.

[0060] Figs 19-21 depict saturation transfer differences (STD) measured by NMR.

[0061] Fig. 20 and 21 depict STD results from acid:choline = 1:1.

[0062] Fig. 22 depicts KD values fitted from STD NMR data.

[0063] Fig. 23 depicts design of a next-generation IL library was based on viscosity, in vivo data, and STD.

[0064] Fig. 24 depicts a schematic of DES-antibody non-specific interactions (hydrophobic, electrostatic) in bulk phase, and manifestation of salting-in and salting-out effect of DES-antibody formulations.

[0065] Figs. 25A-25M depict 6-day biodistribution kinetics for select DES-IgG formulations at 10% DES and 100 mg / mL mouse IgG. Mice (n=5) were injected subcutaneously with a mixture of unmodified and tagged IgG (9.5:0.5). with collected serum extrapolated to a concertation value using a standard curve. Serum AUC p-values and average fluorescent intensity values at the injection site collected via IVIS for all screened candidates used in further experimentation. The images on the bottom of each figure depict mice 6 hours (left) and 14 hours (right) after injection with the IL.

[0066] Figs. 26A-26B depict 21 -day biodistribution kinetics for select DES-IgG formulations at 10% DES and 100 mg / mL mouse IgG. Mice (n=8) were injected subcutaneously with a mixture of unmodified and tagged IgG (9.3:0.7) and analyzed as done previously. Bioavailability is calculated via AUC meaurements as a percentage of IgG administered intravenously (I.V).

[0067] Figs. 27A-27D. Figs. 27A-27C depict 6 day biodistribution kinetics and Fig. 27D depicts 60-day thermal stability for CHexE. 1:2 DES-IgG formulation at 10% DES and 300 mg / mL mouse IgG. Fig. 27D CHexE. 1:2 DES-IgG formulation at 2.5%, 5%, and 10% DES and 300 mg / mL mouse IgG Mice (n=8) were injected subcutaneously with a mi xture of unmodified and tagged IgG (9.5:0.5) and analyzed as done previously. Bioavailability is calculated via AUC meaurements as a percentage of IgG administered intravenously (I.V). CHexE is plotted as dark greay and saline control is plotted as light gray.

[0068] Fig. 28 depict rheological (left) and surface charge data (right) for DES formulated with 300 mg / mL human IgG at a range of concentrations, where formulations with a lower zeta potential values yield a more viscous fluid.

[0069] Fig. 29 depicts extrapolating DES-IgG viscosity measurements (curve marked (1)) via protein-free conductivity measurements (curve marked (2)). Mathematical model (curve marked (3)) was derived from a library of candidate DES-IgG formulations.

[0070] Fig. 30 depicts chemical structures and hydrophobicity indices (logP) of cations and anions deployed in IL synthesis.

[0071] Figs. 31 A-3 IB depict physical characterization of IgG-IL formulations at a concentration of ~90 mg / ml. (Fig. 31 A) Viscosity profiles (n=3) as a function of shear rate for select formulationsCHAi i and CHTJ I . (Fig. 3 IB) Viscosities of IgG-IL formulations at 1 Hz. Lighter bars represent formulations with viscosity < 20 cP and the darker bars represent viscosities > 20 cP. Data are plotted as mean ± SEM.

[0072] Figs. 32A-32C depict thermal stress testing of saline- and IL- formulated high concentration (~90 mg / mL) antibody solutions. (Fig. 32A) Secondary structure and (Fig. 32B) Average aggregate size change after cold-chain storage at 4°C for 7 days of saline and IL fonnulated with IgG antibody. (Fig. 32C) Images of samples exposed to thennal stress conditions in cold and hot chain, with white asterisks indicating samples that formed a solid, gel-like material resultant of aggregation.

[0073] Figs. 33A-33B depict long-term pharmacokinetics of screened IL-IgG formulated at a clinically relevant, high antibody concentration (~90 mg / ml). (Fig. 33A) Serum concentration of exogenous injected IgG as determined via fluorescent intensity of tagged antibody co-formulated with control saline and CMP12 (n=8 / group). (Fig. 33B) Serum area under the curve (AUC) for all tested IL formulations. Lighter bars represent positively screened compositions, while darker bars represent eliminated compositions. Data is plotted as mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 versus saline control using one-way ANOVA.

[0074] Figs. 34A-34D depict thermostability of ultra-high concentration (~230 mg / mL) IgG antibody formulations in CMPi 2. (Fig. 34A) Dependence of viscosity (left) and zeta potential (right) on CMP1 2 concentration in IgG solution (Fig. 34B) Secondary structure and (Fig. 34C) visual aggregation of saline control and 2.5-10% CMP1 2 formulations with IgG following storage at room temperature or 37°C for extended periods (30d,120d). White asterisks indicating samples that formed a solid, gel-like material resultant of aggregation. (Fig. 34D) Binding efficiency of antibody stored in saline control and 2.5-10% (v / v) CMPi:2 for extended period (120d) in cold-chain (4°C), room temperature, or hot-chain (37°C). Data is plotted as mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 using one-way ANOVA.

[0075] Figs. 35A-35B depict long-term pharmacokinetics of screened IL-IgG formulated at an exceeding, ultra-high antibody concentration (~230 mg / ml). (Fig. 35 A) Serum concentration and (Fig. 35B) area under the curve (AUC) of exogenously injected IgG co-formulated with saline control or CMP12 (n=6 / group). Data is plotted as mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 using one-way ANOVA.

[0076] Fig. 36 depicts a list of IL synthesized in initial library screening. Those successfully synthesized are highlighted in dark grey, and those that either precipitated (medium grey) or yielded a strong odor (light grey) during synthesis are denoted separately.

[0077] Fig. 37 depicts a table of aggregate size as a function of room temperature, cold-chain (4°C), and hot-chain (37°C) thermal stress (n=l-3 / group) for ~90 mg / mL samples. NA: not available. Data is represented as mean ± SEM.

[0078] Fig. 38 depicts a table of aggregate size as a function of room temperature, cold-chain (4°C), and hot-chain (37°C) thermal stress (n=l-3 / group) for ~230 mg / mL samples. Data is represented as mean ± SEM.

[0079] Figs. 39A-39C depict physical characterization of neat IL and co-formulated IL with a high concentration antibody (—90 mg / mL) across cation to anion ratios. Viscosity profiles (n=3) as a function of shear rate for all 1 : 1, 2: 1, and 1 :2 IL formulated with a clinically relevant, high concentration of IgG antibody (—90 mg / mL). Anions at higher bounds of alkyl chain length (i.e. heptanoic. C7) in a carboxylic acid structure yielded solid, gel-like materials with high viscosity values poorly suited for injection.

[0080] Figs. 40A-40E depicts secondary structure analysis via circular dichroism for IL-IgG (—90 mg / mL) samples stored at room temperature, cold-chain (4°C), and hot-chain (37°C) for short (Id. 7d) and extended durations (30d).

[0081] Fig. 41 depict antibody melting temperature with physically screened lead IL compositions obtained via differential scanning fluorimetry. Data is represented as mean ± SEM.

[0082] Fig. 42 depicts long-term pharmacokinetics of IL-IgG formulated at a clinically relevant, high antibody concentration (—90 mg / mL). Serum concentration of exogenous injected IgG coformulated with alternative ILs in CHT2: 1, ACHAL 1. CHEL2, and CHALl (n=8 / group). Data is plotted as mean ± SEM.

[0083] Fig. 43 depicts secondary structure analysis via circular dichroism of CMPi 2 IL-IgG (~230 mg / mL) samples stored at room temperature, cold-chain (4°C). and hot-chain (37°C) for extended duration (30d).

[0084] Fig. 44 depicts secondary structure analysis via circular dichroism of CMPI :2 IL-IgG (~230 mg / mL) samples stored at room temperature, cold-chain (4°C). and hot-chain (37°C) for extended duration (120d).

[0085] Fig. 45 depicts local biocompatibility of control and CMPL2 injections. Injection site H&E sections of sham (left), ~230 mg / mL saline (center), and ~230 mg / mL 5% CMPL2 (right). Scale bar: 50pm.

[0086] Fig. 46 depicts systemic biocompatibility of control and CMPI :2 injections. Serum toxicity levels of sham and mice injected subcutaneously with ~230 mg / mL IgG formulated in saline or 5% CMP12. AST: Aspartate Amino Transferase; ALT: Alanine Amino Transferase; BUN: Blood Urea Nitrogen. Reference levels are denoted with horizontal dotted lines. Data is plotted as mean ± SEM.

[0087] Fig. 47 depicts ILs and naming conventions used herein.

[0088] Fig. 48 depicts injection site toxicity of CMP12.

[0089] Fig. 49 depicts serum systemic toxicity of CMP1 2.

[0090] Fig. 50 depicts 100 mg / mL particle size from thermal stress

[0091] Fig. 51 depicts 300 mg / mL particle size from thermal stressDETAILED DESCRIPTION

[0092] The data provided herein demonstrate that certain anions provide superior drug delivery characteristics when combined with a quaternary ammonium cation. Accordingly, in one aspect of any of the embodiments, described herein is a composition comprising at least one ionic liquid comprising 1) an anion which is selected from the group consisting of: hexenoic acid, pentenoic acid, hexanoic acid, methylpentenoic acid, butyric acid, heptanoic acid, dimethylacrylic acid (DMAA); and 2) a cation which is a quaternary ammonium.

[0093] In some embodiments, improved drug delivery characteristics comprise reduced denaturation or degradation of the cargo molecule or active compound. In some embodiments, improved drug delivery characteristics comprise increased ability to cross biological barriers (e.g., increased permeability). In some embodiments of any of the aspects, the improved drug delivery characteristics are for insulin. In some embodiments of any of the aspects, the improved drug delivery characteristics are for large polypeptide (e.g., antibody) cargo molecules (e.g.. active compound). In some embodiments of any of the aspects, the improved drug delivery characteristics are for nucleic acid cargo molecules.

[0094] The term "ionic liquids (ILs)" as used herein refers to organic salts or mixtures of organic salts which are in liquid state at room temperature. This class of solvents has been shown to be useful in a variety of fields, including in industrial processing, catalysis, pharmaceuticals, and electrochemistry. The ionic liquids contain at least one anionic and at least one cationic component. Ionic liquids can comprise an additional hydrogen bond donor (i.e. any molecule that can provide an - OH or an - NH group), examples include but are not limited to alcohols, fatty7acids, and amines. The at least one anionic and at least one cationic component may be present in any molar ratio. Exemplary7molar ratios (catiomanion) include but are not limited to 1 : 1, 1:2, 2: 1, 1 :3, 3: 1, 2:3, 3:2, and ranges between these ratios. For further discussion of ionic liquids, see, e.g., Hough, et al , "Hie third evolution of ionic liquids: active pharmaceutical ingredients", New Journal of Chemistry, 31 : 1429 (2007) and Xu, et al., "Ionic Liquids: Ion Mobilities, Glass Temperatures, and Fragilities", Journal of Physical Chemistry7B, 107(25): 6170-6178 (2003); each of which is incorporated by reference herein in its entirety. In some embodiments of any of the aspects, the ionic liquid or solvent exists as a liquid below 100 °C. In some embodiments of any of the aspects, the ionic liquid or solvent exists as a liquid at room temperature.[0095| In some embodiments of any of the aspects, the ionic liquid comprises a quaternary ammonium cation. In some embodiments of any of the aspects, the cation content of the ionic liquid comprises a quaternary7ammonium. In some embodiments of any of the aspects, the cation content ofthe ionic liquid consists essentially of a quaternary ammonium. In some embodiments of any of the aspects, the cation of the ionic liquid consists of a quaternary ammonium.

[0096] A quarternary ammonium is a positively charged polyatomic ion of the structure NR / , each R independently being an alkyl group or an aryl group. The general term “quaternary ammonium" relates to any compound that can be regarded as derived from ammonium hydroxide or an ammonium salt by replacement of all four hydrogen atoms of the NH i ion by organic groups. For example, the quaternary ammonium has the structure of NR , where each R is independently selected from hydroxyl, optionally substituted Ci-Cioalkyl, optionally substituted C2-Cioalkenyl, optionally substituted C2-Cioalkynyl, optionally substituted aryl, or optionally substituted heteroaryl.

[0097] In some embodiments of any of the aspects, the cation comprises, consists of. or consists essentially of choline. In some embodiments of any of the aspects, the ionic liquid comprises choline. In some embodiments of any of the aspects, the cation content of the ionic liquid comprises choline. In some embodiments of any of the aspects, the cation content of the ionic liquid consists essentially of choline. In some embodiments of any of the aspects, the cation of the ionic liquid consists of choline.

[0098] In some embodiments of any of the aspects, the cation has a molar mass equal to or greater than choline, e.g., a molar mass equal to or greater than 104.1708 g / mol. In some embodiments of any of the aspects, the cation has a molar mass greater than choline, e.g., a molar mass equal greater than 104.1708 g / mol.

[0099] In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an alkyl, alkane, alkene, or aryl, at least one of the R groups comprising an ester. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an alkyl, alkane, or alkene, at least one of the R groups comprising an ester. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an alkane or alkene, at least one of the R groups comprising an ester. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an alkyl, alkane, alkene, or aryl, one of the R groups comprising an ester. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an alkyl, alkane, or alkene, one of the R groups comprising an ester. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an alkane or alkene, one of the R groups comprising an ester.

[0100] In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises a carbon chain of no more than 10 carbon atoms in length, e.g., no more than 10, 11, 12. 13, 14, 15, 16. 17, 18, 19, 20. 25. or 30 carbon atoms in length. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises a carbon chain of no more than 12 carbon atoms in length. In some embodiments of any of the aspects, each Rgroup of the quaternary' ammonium independently comprises a carbon chain of no more than 15 carbon atoms in length. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises a carbon chain of no more than 20 carbon atoms in length.

[0101] In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises a carbon chain of no more than 10 carbon atoms, e.g., no more than 10, 11, 12, 13, 14, 15, 16, 17, 18, 19. 20, 25, or 30 carbon atoms. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises a carbon chain of no more than 12 carbon atoms. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises a carbon chain of no more than 15 carbon atoms. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises a carbon chain of no more than 20 carbon atoms.

[0102] In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an alkyl group of no more than 10 carbon atoms, e.g., no more than 10. 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, or 30 carbon atoms, at least one of the R groups comprising an ester. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an alkyl group of no more than 12 carbon atoms. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an alkyl group of no more than 15 carbon atoms. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an alkyl group of no more than 20 carbon atoms, at least one R group comprising an ester.

[0103] In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an alkane, alkene, aryl, heteroaryl, alkyl, or heteroalkyl, at least one of the R groups comprising an ester. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an unsubstituted alkane, unsubstituted alkene, unsubstituted ary l, unsubstituted heteroaryl, unsubstituted alkyl, or unsubstituted heteroalkyl, , at least one of the R groups comprising an ester. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises an unsubstituted alkane, at least one of the R groups comprising an ester. In some embodiments of any of the aspects, each R group of the quaternary' ammonium independently comprises an unsubstituted alkene, at least one of the R groups comprising an ester. In some embodiments of any of the aspects, each R group of the quaternary ammonium independently comprises one or more substituent groups, at least one of the R groups comprising an ester.

[0104] In some embodiments of any of the aspects, at least one R group of the quaternary ammonium comprises a hydroxy group, at least one of the R groups comprising an ester. In some embodiments of any of the aspects, one R group of the quaternary ammonium comprises a hydroxy' group, at least one of the R groups comprising an ester. In some embodiments of any of the aspects,only one R group of the quaternary ammonium comprises a hydroxy group, at least one of the R groups comprising an ester.

[0105] In some embodiments of any of the aspects, three of the R groups are methyl, and one R group of the quaternary' ammonium comprises an ester, e.g., acetylcholine. In some embodiments of any of the aspects, the cation comprises, consists of, or consists essentially of acetylcholine. In some embodiments of any of the aspects, the cation comprises, consists of, or consists essentially of methacholine.

[0106] In some embodiments of any of the aspects, the cation comprises, consists of, or consists essentially of choline, acetylcholine, and / or methacholine. In some embodiments of any of the aspects, the ionic liquid comprises choline, acetylcholine, and / or methacholine. In some embodiments of any of the aspects, the cation content of the ionic liquid comprises choline, acetylcholine, and / or methacholine. In some embodiments of any of the aspects, the cation content of the ionic liquid consists essentially of choline, acetylcholine, and / or methacholine. In some embodiments of any of the aspects, the cation of the ionic liquid consists of choline, acetylcholine, and / or methacholine.

[0107] In some embodiments of any of the aspects, the cation comprises, consists of, or consists essentially of acetylcholine. In some embodiments of any of the aspects, the ionic liquid comprises acetylcholine. In some embodiments of any of the aspects, the cation content of the ionic liquid comprises acetylcholine. In some embodiments of any of the aspects, the cation content of the ionic liquid consists essentially of acetylcholine. In some embodiments of any of tire aspects, the cation of the ionic liquid consists of acetylcholine.

[0108] In some embodiments of any of the aspects, the cation comprises, consists of, or consists essentially of methacholine. In some embodiments of any of the aspects, the ionic liquid comprises methacholine. In some embodiments of any of the aspects, the cation content of the ionic liquid comprises methacholine. In some embodiments of any of the aspects, the cation content of the ionic liquid consists essentially of methacholine. In some embodiments of any of the aspects, the cation of the ionic liquid consists of methacholine.Formula V; metlracholine

[0109] In some embodiments of any of the aspects, the anion is selected from the group consisting of: hexenoic acid, pentenoic acid, hexanoic acid, methylpentenoic acid, butyric acid, heptanoic acid, dimethylacrylic acid (DMAA); lactic acid; glycolic acid; gluconic acid; glutaric acid; tartaric acid; citric acid; and EDTA.Formula VII (pentenoic acid)Formula IX (methylpentenoic acid. i.e.. 4-methyl 2-Pentenoic acid)Formula XI (heptanoic acid)Formula XII (dimethylacrylic acid)Formula XII (lactic acid)Formula XV (gluconic acid)Formula XVII (tartaric acid)Formula XIX (Ethylenediaminetetraacetic acid (EDTA))

[0110] In some embodiments of any of the aspects, the anion is selected from the group consisting of: hexenoic acid, hexanoic acid, methylpentenoic acid, and heptanoic acid. In some embodiments of any of the aspects, the anion is selected from the group consisting of: hexanoic acid,mcthylpcntcnoic acid, and hcptanoic acid. In some embodiments of any of the aspects, the anion is selected from the group consisting of: hexanoic acid and methylpentenoic acid. In some embodiments of any of the aspects, the anion is selected from the group consisting of: methylpentenoic acid and heptanoic acid.

[0111] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of: choline hexanoic acid; choline heptanoic acid; choline methylpentenoic acid; choline hexenoic acid: acetylcholine hexanoic acid; and methacholine hexenoic acid. In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of: choline hexanoic acid; choline heptanoic acid; choline methylpentenoic acid; choline hexenoic acid; and acetylcholine hexanoic acid. In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of: choline hexanoic acid; choline heptanoic acid; and choline methylpentenoic acid. In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of: choline hexanoic acid; choline heptanoic acid: choline methylpentenoic acid; choline hexenoic acid; and methacholine hexenoic acid. In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of: choline hexanoic acid and choline methylpentenoic acid. In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of: choline hexenoic acid and choline methylpentenoic acid. In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of: choline hexanoic acid; choline methylpentenoic acid; and choline hexenoic acid. In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of: lactic acid: glycolic acid; gluconic acid; glutaric acid; tartaric acid; citric acid; and EDTA. In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of: glutaric acid and EDTA.

[0112] In some embodiments of any of the aspects, the at least one ionic liquid is choline hexanoic acid. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline hexanoic acid. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of choline hexanoic acid. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline hexanoic acid. In some embodiments of any of the aspects, the ionic liquid is choline hexanoic acid. In some embodiments of any of the aspects, the ionic liquid comprises choline hexanoic acid. In some embodiments of any of the aspects, the ionic liquid consists essentially of choline hexanoic acid. In some embodiments of any of the aspects, tire ionic liquid consists of choline hexanoic acid. In some embodiments of any of the aspects, the first ionic liquid is choline hexanoic acid. In some embodiments of any of the aspects, the first ionic liquid comprises choline hexanoic acid. In some embodiments of any of the aspects, the first ionic liquid consists essentially of choline hexanoic acid. In some embodiments of any of the aspects, the first ionic liquid consists of choline hexanoic acid.

[0113] In some embodiments of any of the aspects, the at least one ionic liquid is choline heptanoic acid. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline heptanoic acid. In some embodiments of any of tire aspects, the at least one ionic liquid consists essentially of choline heptanoic acid. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline heptanoic acid. In some embodiments of any of the aspects, the ionic liquid is choline heptanoic acid. In some embodiments of any of the aspects, the ionic liquid comprises choline heptanoic acid. In some embodiments of any of the aspects, the ionic liquid consists essentially of choline heptanoic acid. In some embodiments of any of the aspects, the ionic liquid consists of choline heptanoic acid. In some embodiments of any of the aspects, the first ionic liquid is choline heptanoic acid. In some embodiments of any of the aspects, the first ionic liquid comprises choline heptanoic acid. In some embodiments of any of the aspects, the first ionic liquid consists essentially of choline heptanoic acid. In some embodiments of any of the aspects, the first ionic liquid consists of choline heptanoic acid.

[0114] In some embodiments of any of the aspects, the at least one ionic liquid is choline methylpentenoic acid. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline methylpentenoic acid. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of choline methylpentenoic acid. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline methylpentenoic acid. In some embodiments of any of the aspects, the ionic liquid is choline methylpentenoic acid. In some embodiments of any of the aspects, the ionic liquid comprises choline methylpentenoic acid. In some embodiments of any of the aspects, the ionic liquid consists essentially of choline methylpentenoic acid. In some embodiments of any of the aspects, the ionic liquid consists of choline methylpentenoic acid. In some embodiments of any of the aspects, the first ionic liquid is choline methylpentenoic acid. In some embodiments of any of the aspects, the first ionic liquid comprises choline methylpentenoic acid. In some embodiments of any of the aspects, the first ionic liquid consists essentially of choline methylpentenoic acid. In some embodiments of any of the aspects, the first ionic liquid consists of choline methylpentenoic acid.

[0115] In some embodiments of any of the aspects, the at least one ionic liquid is choline hexenoic acid. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline hexenoic acid. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of choline hexenoic acid. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline hexenoic acid. In some embodiments of any of the aspects, the ionic liquid is choline hexenoic acid. In some embodiments of any of the aspects, the ionic liquid comprises choline hexenoic acid. In some embodiments of any of the aspects, the ionic liquid consists essentially of choline hexenoic acid. In some embodiments of any of the aspects, the ionic liquid consists of choline hexenoic acid. In some embodiments of any of the aspects, the first ionic liquid ischoline hcxcnoic acid. In some embodiments of any of the aspects, the first ionic liquid comprises choline hexenoic acid. In some embodiments of any of the aspects, the first ionic liquid consists essentially of choline hexenoic acid. In some embodiments of any of the aspects, the first ionic liquid consists of choline hexenoic acid.

[0116] In some embodiments of any of the aspects, the at least one ionic liquid is acetylcholine hexanoic acid. In some embodiments of any of the aspects, the at least one ionic liquid comprises acetylcholine hexanoic acid. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of acetylcholine hexanoic acid. In some embodiments of any of the aspects, the at least one ionic liquid consists of acetylcholine hexanoic acid. In some embodiments of any of the aspects, the ionic liquid is acety lcholine hexanoic acid. In some embodiments of any of the aspects, the ionic liquid comprises acety lcholine hexanoic acid. In some embodiments of any of the aspects, the ionic liquid consists essentially of acetylcholine hexanoic acid. In some embodiments of any of the aspects, the ionic liquid consists of acety lcholine hexanoic acid. In some embodiments of any of the aspects, the first ionic liquid is acety lcholine hexanoic acid. In some embodiments of any of the aspects, the first ionic liquid comprises acetylcholine hexanoic acid. In some embodiments of any of the aspects, the first ionic liquid consists essentially of acetylcholine hexanoic acid. In some embodiments of any of the aspects, the first ionic liquid consists of acetylcholine hexanoic acid.

[0117] In some embodiments of any of the aspects, the at least one ionic liquid is methacholine hexenoic acid. In some embodiments of any of the aspects, the at least one ionic liquid comprises methacholine hexenoic acid. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of methacholine hexenoic acid. In some embodiments of any of the aspects, the at least one ionic liquid consists of methacholine hexenoic acid. In some embodiments of any of the aspects, the ionic liquid is methacholine hexenoic acid. In some embodiments of any of the aspects, the ionic liquid comprises methacholine hexenoic acid. In some embodiments of any of the aspects, the ionic liquid consists essentially of methacholine hexenoic acid. In some embodiments of any of the aspects, the ionic liquid consists of methacholine hexenoic acid. In some embodiments of any of the aspects, the first ionic liquid is methacholine hexenoic acid. In some embodiments of any of the aspects, the first ionic liquid comprises methacholine hexenoic acid. In some embodiments of any of the aspects, the first ionic liquid consists essentially of methacholine hexenoic acid. In some embodiments of any of the aspects, the first ionic liquid consists of methacholine hexenoic acid.

[0118] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a catiomanion ratio of 2: 1;Choline methylpentenoic acid at a cation:anion ratio of 1:2:Choline hexenoic acid at a catiomanion ratio of 1 :2;Acetylcholine hexanoic acid at a cation: anion ratio of 1 : 1 ; and Methacholine hexenoic acid at a cation: anion ratio of 1 : 1.

[0119] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a catiomanion ratio of 2:1;Choline methylpentenoic acid at a catiomanion ratio of 1:2:Choline hexenoic acid at a catiomanion ratio of 1 :2; and Acetylcholine hexanoic acid at a cation: anion ratio of 1 : 1.

[0120] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a catiomanion ratio of 2: 1; andCholine methylpentenoic acid at a catiomanion ratio of 1 :2.

[0121] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1:1;Choline heptanoic acid at a catiomanion ratio of 2:1;Choline methylpentenoic acid at a catiomanion ratio of 1 :2;Choline hexenoic acid at a catiomanion ratio of 1 :2; and Methacholine hexenoic acid at a cation: anion ratio of 1 : 1.

[0122] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline methylpentenoic acid at a catiomanion ratio of 1:2; andCholine hexenoic acid at a catiomanion ratio of 1 :2.

[0123] In some embodiments of any of the aspects, the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline methylpentenoic acid at a catiomanion ratio of 1:2: andCholine hexenoic acid at a catiomanion ratio of 1 :2.

[0124] In some embodiments of any of the aspects, the at least one ionic liquid is choline hexanoic acid at a catiomanion ratio of 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline hexanoic acid at a catiomanion ratio of 1: 1. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of choline hexanoic acid at a cation: anion ratio of 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline hexanoic acid at a catiomanion ratio of 1: 1. In some embodiments of any of theaspects, the ionic liquid is choline hexanoic acid at a cation:anion ratio of 1:1. In some embodiments of any of the aspects, the ionic liquid comprises choline hexanoic acid at a cation:anion ratio of 1:1. In some embodiments of any of the aspects, the ionic liquid consists essentially of choline hexanoic acid at a catiomanion ratio of 1:1. In some embodiments of any of the aspects, the ionic liquid consists of choline hexanoic acid at a cation:anion ratio of 1:1. In some embodiments of any of the aspects, the first ionic liquid is choline hexanoic acid at a catiomanion ratio of 1 : 1. In some embodiments of any of the aspects, the first ionic liquid comprises choline hexanoic acid at a catiomanion ratio of 1:1. In some embodiments of any of the aspects, the first ionic liquid consists essentially of choline hexanoic acid at a catiomanion ratio of 1:1. In some embodiments of any of the aspects, the first ionic liquid consists of choline hexanoic acid at a cation:anion ratio of 1: 1.

[0125] In some embodiments of any of the aspects, the at least one ionic liquid is choline hexanoic acid at a cation:anion ratio of about 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline hexanoic acid at a cation: anion ratio of about 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of choline hexanoic acid at a cation:anion ratio of about 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline hexanoic acid at a cation:anion ratio of about 1:1. In some embodiments of any of the aspects, the ionic liquid is choline hexanoic acid at a cation: anion ratio of about 1 : 1. In some embodiments of any of the aspects, the ionic liquid comprises choline hexanoic acid at a catiomanion ratio of about 1 : 1 . In some embodiments of any of the aspects, the ionic liquid consists essentially of choline hexanoic acid at a catiomanion ratio of about 1:1. In some embodiments of any of the aspects, the ionic liquid consists of choline hexanoic acid at a catiomanion ratio of about 1: 1. In some embodiments of any of the aspects, the first ionic liquid is choline hexanoic acid at a catiomanion ratio of about 1:1. In some embodiments of any of the aspects, the first ionic liquid comprises choline hexanoic acid at a catiomanion ratio of about 1:1. In some embodiments of any of the aspects, the first ionic liquid consists essentially of choline hexanoic acid at a catiomanion ratio of about 1 : 1. In some embodiments of any of the aspects, the first ionic liquid consists of choline hexanoic acid at a catiomanion ratio of about 1:1.

[0126] In some embodiments of any of the aspects, the at least one ionic liquid is acetylcholine hexanoic acid at a catiomanion ratio of 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid comprises acetylcholine hexanoic acid at a catiomanion ratio of 1:1. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of acetylcholine hexanoic acid at a catiomanion ratio of 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid consists of acetylcholine hexanoic acid at a cation: anion ratio of 1:1. In some embodiments of any of the aspects, the ionic liquid is acetylcholine hexanoic acid at a catiomanion ratio of 1:1. In some embodiments of any of the aspects, the ionic liquid comprises acetylcholine hexanoic acid at a catiomanion ratio of 1:1. In some embodiments of any of the aspects, the ionicliquid consists essentially of acetylcholine hexanoic acid at a cation:anion ratio of 1:1. In some embodiments of any of the aspects, the ionic liquid consists of acetylcholine hexanoic acid at a cation: anion ratio of 1:1. In some embodiments of any of the aspects, the first ionic liquid is acetylcholine hexanoic acid at a cation:anion ratio of 1:1. In some embodiments of any of the aspects, the first ionic liquid comprises acetylcholine hexanoic acid at a catiomanion ratio of 1 : 1. In some embodiments of any of the aspects, the first ionic liquid consists essentially of acetylcholine hexanoic acid at a cation :anion ratio of 1:1. In some embodiments of any of the aspects, the first ionic liquid consists of acetylcholine hexanoic acid at a cation:anion ratio of 1:1.

[0127] In some embodiments of any of the aspects, the at least one ionic liquid is acetylcholine hexanoic acid at a cation:anion ratio of about 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid comprises acetylcholine hexanoic acid at a cation:anion ratio of about 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of acetylcholine hexanoic acid at a cation:anion ratio of about 1:1. In some embodiments of any of the aspects, the at least one ionic liquid consists of acetylcholine hexanoic acid at a cation:anion ratio of about 1 : 1. In some embodiments of any of the aspects, the ionic liquid is acetylcholine hexanoic acid at a cation:anion ratio of about 1 : 1. In some embodiments of any of the aspects, the ionic liquid comprises acetylcholine hexanoic acid at a cation:anion ratio of about 1:1. In some embodiments of any of the aspects, the ionic liquid consists essentially of acetylcholine hexanoic acid at a cation:anion ratio of about 1: 1. In some embodiments of any of the aspects, the ionic liquid consists of acetylcholine hexanoic acid at a cation:anion ratio of about 1:1. In some embodiments of any of the aspects, the first ionic liquid is acetylcholine hexanoic acid at a catiomanion ratio of about 1:1. In some embodiments of any of the aspects, the first ionic liquid comprises acetylcholine hexanoic acid at a catiomanion ratio of about 1:1. In some embodiments of any of the aspects, the first ionic liquid consists essentially of acetylcholine hexanoic acid at a cation :anion ratio of about 1:1. In some embodiments of any of the aspects, the first ionic liquid consists of acetylcholine hexanoic acid at a cation: anion ratio of about 1:1.

[0128] In some embodiments of any of the aspects, the at least one ionic liquid is methacholine hexenoic acid at a cation :anion ratio of 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid comprises methacholine hexenoic acid at a catiomanion ratio of 1:1. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of methacholine hexenoic acid at a cation:anion ratio of 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid consists of methacholine hexenoic acid at a catioiramon ratio of 1 : 1. In some embodiments of any of the aspects, the ionic liquid is methacholine hexenoic acid at a cation:anion ratio of 1:1. In some embodiments of any of the aspects, the ionic liquid comprises methacholine hexenoic acid at a cation:anion ratio of 1:1. In some embodiments of any of the aspects, the ionic liquid consists essentially of methacholine hexenoic acid at a cation: anion ratio of 1:1. In someembodiments of any of the aspects, the ionic liquid consists of mcthacholinc hcxcnoic acid at a cation: anion ratio of 1:1. In some embodiments of any of the aspects, the first ionic liquid is methacholine hexenoic acid at a cation: anion ratio of 1 : 1. In some embodiments of any of the aspects, the first ionic liquid comprises methacholine hexenoic acid at a catiomanion ratio of 1:1. In some embodiments of any of the aspects, the first ionic liquid consists essentially of methacholine hexenoic acid at a catiomanion ratio of 1:1. In some embodiments of any of the aspects, the first ionic liquid consists of methacholine hexenoic acid at a cation:anion ratio of 1 : 1.

[0129] In some embodiments of any of the aspects, the at least one ionic liquid is methacholine hexenoic acid at a cation:anion ratio of about 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid comprises methacholine hexenoic acid at a cation:anion ratio of about 1:1. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of methacholine hexenoic acid at a cation:anion ratio of about 1 : 1. In some embodiments of any of the aspects, the at least one ionic liquid consists of methacholine hexenoic acid at a cation: anion ratio of about 1 : 1. In some embodiments of any of the aspects, the ionic liquid is methacholine hexenoic acid at a cation:anion ratio of about 1 : 1. In some embodiments of any of the aspects, the ionic liquid comprises methacholine hexenoic acid at a cation:anion ratio of about 1: 1. In some embodiments of any of the aspects, the ionic liquid consists essentially of methacholine hexenoic acid at a cation :anion ratio of about 1: 1. In some embodiments of any of the aspects, the ionic liquid consists of methacholine hexenoic acid at a cation:anion ratio of about 1:1. In some embodiments of any of the aspects, the first ionic liquid is methacholine hexenoic acid at a catiomanion ratio of about 1 : 1. In some embodiments of any of the aspects, the first ionic liquid comprises methacholine hexenoic acid at a cation: an ion ratio of about 1:1. In some embodiments of any of the aspects, the first ionic liquid consists essentially of methacholine hexenoic acid at a catiomanion ratio of about 1:1. In some embodiments of any of the aspects, the first ionic liquid consists of methacholine hexenoic acid at a cation: anion ratio of about 1:1.

[0130] In some embodiments of any of the aspects, the at least one ionic liquid is choline heptanoic acid at a catiomanion ratio of 2: 1. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline heptanoic acid at a catiomanion ratio of 2: 1. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of choline heptanoic acid at a cation: anion ratio of 2 : 1. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline heptanoic acid at a catiomanion ratio of 2: 1. In some embodiments of any of the aspects, the ionic liquid is choline heptanoic acid at a catiomanion ratio of 2: 1. In some embodiments of any of the aspects, the ionic liquid comprises choline heptanoic acid at a catiomanion ratio of 2: 1. In some embodiments of any of the aspects, the ionic liquid consists essentially of choline heptanoic acid at a catiomanion ratio of 2: 1. In some embodiments of any of the aspects, the ionic liquid consists of choline heptanoic acid at a catiomanion ratio of 2: 1. In some embodiments of any of the aspects.the first ionic liquid is choline hcptanoic acid at a cation:anion ratio of 2:1. In some embodiments of any of the aspects, the first ionic liquid comprises choline heptanoic acid at a cation:anion ratio of 2: 1. In some embodiments of any of tire aspects, the first ionic liquid consists essentially of choline heptanoic acid at a catiomanion ratio of 2: 1. In some embodiments of any of the aspects, the first ionic liquid consists of choline heptanoic acid at a catiomanion ratio of 2: 1.

[0131] In some embodiments of any of the aspects, the at least one ionic liquid is choline heptanoic acid at a catiomanion ratio of about 2:1. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline heptanoic acid at a cation:anion ratio of about 2:1. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of choline heptanoic acid at a catiomanion ratio of about 2:1. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline heptanoic acid at a cation:anion ratio of about 2:1. In some embodiments of any of the aspects, the ionic liquid is choline heptanoic acid at a catiomanion ratio of about 2:1. In some embodiments of any of the aspects, the ionic liquid comprises choline heptanoic acid at a cation:anion ratio of about 2:1. In some embodiments of any of the aspects, the ionic liquid consists essentially of choline heptanoic acid at a cation:anion ratio of about 2:1. In some embodiments of any of the aspects, the ionic liquid consists of choline heptanoic acid at a catiomanion ratio of about 2: 1. In some embodiments of any of the aspects, the first ionic liquid is choline heptanoic acid at a catiomanion ratio of about 2:1. In some embodiments of any of the aspects, the first ionic liquid comprises choline heptanoic acid at a catiomanion ratio of about 2:1. In some embodiments of any of the aspects, the first ionic liquid consists essentially of choline heptanoic acid at a catiomanion ratio of about 2: 1. In some embodiments of any of the aspects, the first ionic liquid consists of choline heptanoic acid at a catiomanion ratio of about 2:1.

[0132] In some embodiments of any of the aspects, the at least one ionic liquid is choline hexenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline hexenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of choline hexenoic acid at a catiomanion ratio of 1 :2. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline hexenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the ionic liquid is choline hexenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the ionic liquid comprises choline hexenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the ionic liquid consists essentially of choline hexenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the ionic liquid consists of choline hexenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the first ionic liquid is choline hexenoic acid at a catiomanion ratio of 1 :2. In some embodiments of any of the aspects, the first ionic liquid comprises choline hexenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the first ionic liquid consists essentially of choline hexenoicacid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the first ionic liquid consists of choline hexenoic acid at a catiomanion ratio of 1:2.

[0133] In some embodiments of any of the aspects, the at least one ionic liquid is choline hexenoic acid at a catiomanion ratio of about 1 :2. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline hexenoic acid at a catiomanion ratio of about 1 :2. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of choline hexenoic acid at a catiomanion ratio of about 1 :2. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline hexenoic acid at a catiomanion ratio of about 1:2. In some embodiments of any of the aspects, the ionic liquid is choline hexenoic acid at a cation: anion ratio of about 1:2. In some embodiments of any of the aspects, the ionic liquid comprises choline hexenoic acid at a catiomanion ratio of about 1:2. In some embodiments of any of the aspects, the ionic liquid consists essentially of choline hexenoic acid at a catiomanion ratio of about 1:2. In some embodiments of any of the aspects, the ionic liquid consists of choline hexenoic acid at a catiomanion ratio of about 1:2. In some embodiments of any of the aspects, the first ionic liquid is choline hexenoic acid at a catiomanion ratio of about 1:2. In some embodiments of any of the aspects, the first ionic liquid comprises choline hexenoic acid at a catiomanion ratio of about 1:2. In some embodiments of any of the aspects, the first ionic liquid consists essentially of choline hexenoic acid at a catiomanion ratio of about 1 :2. In some embodiments of any of the aspects, the first ionic liquid consists of choline hexenoic acid at a catiomanion ratio of about 1:2.

[0134] In some embodiments of any of the aspects, the at least one ionic liquid is choline methylpentenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline methylpentenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of choline methy lpentenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline methylpentenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the ionic liquid is choline methylpentenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the ionic liquid comprises choline methylpentenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the ionic liquid consists essentially of choline methylpentenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the ionic liquid consists of choline methylpentenoic acid at a cation: anion ratio of 1 :2. In some embodiments of any of the aspects, the first ionic liquid is choline methylpentenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the first ionic liquid comprises choline methylpentenoic acid at a catiomanion ratio of 1 :2. In some embodiments of any of the aspects, the first ionic liquid consists essentially of choline methylpentenoic acid at a catiomanion ratio of 1:2. In some embodiments of any of the aspects, the first ionic liquid consists of choline methylpentenoic acid at a catiomanion ratio of 1:2.

[0135] In some embodiments of any of the aspects, the at least one ionic liquid is choline methylpentenoic acid at a cation ianion ratio of about 1:2. In some embodiments of any of the aspects, the at least one ionic liquid comprises choline methylpentenoic acid at a cation: anion ratio of about 1:2. In some embodiments of any of the aspects, the at least one ionic liquid consists essentially of choline methylpentenoic acid at a catiomanion ratio of about 1 :2. In some embodiments of any of the aspects, the at least one ionic liquid consists of choline methylpentenoic acid at a catiomanion ratio of about 1 :2. In some embodiments of any of the aspects, the ionic liquid is choline methylpentenoic acid at a cation:anion ratio of about 1:2. In some embodiments of any of the aspects, the ionic liquid comprises choline methylpentenoic acid at a cation:anion ratio of about 1 :2. In some embodiments of any of the aspects, the ionic liquid consists essentially of choline methylpentenoic acid at a catiomanion ratio of about 1 :2. In some embodiments of any of the aspects, the ionic liquid consists of choline methylpentenoic acid at a catioiranion ratio of about 1 :2. In some embodiments of any of the aspects, the first ionic liquid is choline methylpentenoic acid at a catiomanion ratio of about 1:2. In some embodiments of any of the aspects, the first ionic liquid comprises choline methylpentenoic acid at a catiomanion ratio of about 1 :2. In some embodiments of any of the aspects, the first ionic liquid consists essentially of choline methylpentenoic acid at a catiomanion ratio of about 1 :2. In some embodiments of any of the aspects, the first ionic liquid consists of choline methylpentenoic acid at a catiomanion ratio of about 1 :2.

[0136] In some embodiments of any of the aspects, the at least one ionic liquid is not CAGE (Choline And GEranate). In some embodiments of any of the aspects, the cation of the at least one ionic liquid is not choline. In some embodiments of any of the aspects, the anion of the at least one ionic liquid is not geranate or geranic acid.

[0137] In some embodiments of any of the aspects, the first ionic liquid is not CAGE (Choline And GEranate). In some embodiments of any of the aspects, the cation of the first ionic liquid is not choline. In some embodiments of any of the aspects, the anion of the first ionic liquid is not geranate or geranic acid.

[0138] In some embodiments of any of the aspects, the IL is at a concentration of at least 0.01% w / v. In some embodiments of any of the aspects, the IL is at a concentration of at least 0.05% w / v. In some embodiments of any of tire aspects, the IL is at a concentration of at least 0.1% w / v. In some embodiments of any of the aspects, the IL is at a concentration of at least 0.2% w / v, at least 0.3% w / v, at least 0.4% w / v, at least 0.5% w / v, at least 1% w / v or greater. In some embodiments of any of the aspects, the IL is at a concentration of from about 0.01% w / v to about 1% w / v. In some embodiments of any of the aspects, the IL is at a concentration of from 0.01% w / v to 1% w / v. In some embodiments of any of the aspects, the IL is at a concentration of from about 0.05% w / v to about 0.5% w / v. In some embodiments of any of the aspects, the IL is at a concentration of from 0.05% w / v to 0.5% w / v.

[0139] In some embodiments of any of the aspects, the IL is at a concentration of less than 10% w / v. In some embodiments of any of the aspects, the IL is at a concentration of from 0.01% w / v to 10% w / v. In some embodiments of any of the aspects, the IL is at a concentration of from 0.05% w / v to 10% w / v. In some embodiments of any of the aspects, the IL is at a concentration of from 0.5% w / v to 10% w / v. hi some embodiments of any of the aspects, the IL is at a concentration of from 1% w / v to 10% w / v.

[0140] In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 10%v / v. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 10%v / v. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 5%v / v. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 5%v / v. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 15%v / v. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 15%v / v. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 20%v / v. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 20%v / v.

[0141] In some embodiments of any of the aspects, the IL is at a concentration of at least l%v / v. In some embodiments of any of the aspects, the IL is at a concentration of at least 2%v / v. In some embodiments of any of the aspects, the IL is at a concentration of less than 10% v / v. In some embodiments of any of the aspects, the IL is at a concentration of less than 15% v / v. In some embodiments of any of the aspects, the IL is at a concentration of less than 20% v / v.

[0142] In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 10%v / v in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 10%v / v in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 5%v / v in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 5%v / v in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 15%v / v in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 15%v / v in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 20%v / v in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 20%v / v in saline or a physiologically compatible buffer.

[0143] In some embodiments of any of the aspects, the IL is at a concentration of at least l%v / v in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of at least 2%v / v in saline or a physiologically compatible buffer. In someembodiments of any of the aspects, the IL is at a concentration of less than 10% v / v in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of less than 15% v / v in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of less than 20% v / v in saline or a physiologically compatible buffer.

[0144] In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 10%v / v in saline. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 10%v / v in saline. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 5%v / v in saline. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 5%v / v in saline. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 15%v / v in saline. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 15%v / v in saline. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 20%v / v in saline. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 20%v / v in saline.

[0145] In some embodiments of any of the aspects, the IL is at a concentration of at least l%v / v in saline. In some embodiments of any of the aspects, the IL is at a concentration of at least 2%v / v in saline. In some embodiments of any of the aspects, the IL is at a concentration of less than 10% v / v in saline. In some embodiments of any of the aspects, the IL is at a concentration of less than 15% v / v in saline. In some embodiments of any of the aspects, the IL is at a concentration of less than 20% v / v in saline.

[0146] In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 10%v / v in a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 10%v / v in a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 5%v / v in a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 5%v / v in a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 15%v / v in a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 15%v / v in a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 to about 20%v / v in a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of from 1 to 20%v / v in a physiologically compatible buffer.

[0147] In some embodiments of any of the aspects, the IL is at a concentration of at least l%v / v in a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of at least 2%v / v in a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of less than 10% v / v in a physiologically compatible buffer.In some embodiments of any of the aspects, the IL is at a concentration of less than 15% v / v in a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of less than 20% v / v in a physiologically compatible buffer.

[0148] In some embodiments of any of the aspects, the IL is at a concentration of at least about 10% w / w. In some embodiments of any of the aspects, the IL is at a concentration of at least about 10% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of at least about 10% w / w in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of at least 10% w / w. In some embodiments of any of the aspects, the IL is at a concentration of at least 10% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of at least 10% w / w in saline or a physiologically compatible buffer.

[0149] In some embodiments of any of the aspects, the IL is at a concentration of at least about 15% w / w. In some embodiments of any of the aspects, the IL is at a concentration of at least about 15% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of at least about 15% w / w in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of at least 15% w / w. In some embodiments of any of the aspects, the IL is at a concentration of at least 15% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of at least 15% w / w in saline or a physiologically compatible buffer.

[0150] In some embodiments of any of the aspects, the IL is at a concentration of at least about 20% w / w. In some embodiments of any of the aspects, the IL is at a concentration of at least about 20% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of at least about 20% w / w in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of at least 20% w / w. In some embodiments of any of the aspects, the IL is at a concentration of at least 20% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of at least 20% w / w in saline or a physiologically compatible buffer.

[0151] In some embodiments of any of the aspects, the IL is at a concentration of about 10% to about 70% w / w. In some embodiments of any of the aspects, the IL is at a concentration of about 10% to about 70% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of about 10% to about 70% w / w in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of 10% to 70% w / w. In some embodiments of any of the aspects, the IL is at a concentration of 10% to 70% in water. In some embodiments of any of the aspects, the IL is at a concentration of 10% to 70% w / w in saline or a physiologically compatible buffer.

[0152] In some embodiments of any of the aspects, the IL is at a concentration of about 10% to about 40% w / w. In some embodiments of any of the aspects, the IL is at a concentration of about 10% to about 40% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of about 10% to about 40% w / w in saline or a physiologically compatible buffer. Insome embodiments of any of the aspects, the IL is at a concentration of 10% to 40% w / w. In some embodiments of any of the aspects, the IL is at a concentration of 10% to 40% in water. In some embodiments of any of the aspects, the IL is at a concentration of 10% to 40% w / w in saline or a physiologically compatible buffer.

[0153] In some embodiments of any of the aspects, the IL is at a concentration of about 10% to about 30% w / w. In some embodiments of any of the aspects, the IL is at a concentration of about 10% to about 30% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of about 10% to about 30% w / w in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of 10% to 30% w / w. In some embodiments of any of the aspects, the IL is at a concentration of 10% to 30% in water. In some embodiments of any of the aspects, the IL is at a concentration of 10% to 30% w / w in saline or a physiologically compatible buffer.

[0154] In some embodiments of any of the aspects, the IL is at a concentration of about 20% to about 40% w / w. In some embodiments of any of the aspects, the IL is at a concentration of about 20% to about 40% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of about 20% to about 40% w / w in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of 20% to 40% w / w. In some embodiments of any of the aspects, the IL is at a concentration of 20% to 40% in water. In some embodiments of any of the aspects, the IL is at a concentration of 20% to 40% w / w in saline or a physiologically compatible buffer.

[0155] In some embodiments of any of the aspects, the IL is at a concentration of about 20% to about 30% w / w. In some embodiments of any of the aspects, the IL is at a concentration of about 20% to about 30% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of about 20% to about 30% w / w in saline or a physiologically compatible buffer. In some embodiments of any of the aspects, the IL is at a concentration of 20% to 30% w / w. In some embodiments of any of the aspects, the IL is at a concentration of 20% to 30% in water. In some embodiments of any of the aspects, the IL is at a concentration of 20% to 30% w / w in saline or a physiologically compatible buffer.

[0156] In some embodiments of any of the aspects, the IL is at a concentration of at least 25% w / w. In some embodiments of any of the aspects, the IL is at a concentration of at least 25% w / w in water. In some embodiments of any of the aspects, the IL is at a concentration of at least 25% w / w in saline or a physiologically compatible buffer.

[0157] In some embodiments of any of the aspects, the IL is at a concentration of from about 5% w / w to about 75% w / w. In some embodiments of any of the aspects, the IL is at a concentration of from 5% w / w to 75% w / w. In some embodiments of any of the aspects, the IL is at a concentration of from about 5% w / w to about 75% w / w in water, saline or a physiologically compatible buffer. Insome embodiments of any of the aspects, the IL is at a concentration of from 5% w / w to 75% w / w in water, saline or a physiologically compatible buffer.

[0158] In some embodiments of any of the aspects, the IL is at a concentration of at least about 0.1 % w / w. In some embodiments of any of the aspects, the IL is at a concentration of at least 0.1 % w / w. In some embodiments of any of the aspects, the IL is at a concentration of from about 10 % w / w to about 70 % w / w. In some embodiments of any of the aspects, the IL is at a concentration of from 10 % w / w to 70 % w / w. In some embodiments of any of the aspects, the IL is at a concentration of from about 30 % w / w to about 50 % w / w. In some embodiments of any of the aspects, the IL is at a concentration of from 30 % w / w to 40 % w / w. In some embodiments of any of the aspects, the IL is at a concentration of from about 30 % w / w to about 50 % w / w. In some embodiments of any of the aspects, the IL is at a concentration of from 30 % w / w to 40 % w / w.

[0159] In some embodiments of any of the aspects, the % w / w concentration of the IL is % w / w concentration in water, saline, or a physiologically compatible buffer.

[0160] In some embodiments of any of the aspects, the IL is 100% by w / w or w / v.

[0161] In some embodiments, the IL is an anhydrous salt, e.g.. an ionic liquid not diluted or dissolved in water. In some embodiments, the IL is provided as an aqueous solution.

[0162] In some embodiments of any of the aspects, the IL is at a concentration of at least 25% w / w and has a ratio of catiomanion of at least 1:3. In some embodiments of any of the aspects, the IL is at a concentration of at least 25% w / w in water and has a ratio of catiomanion of at least 1 :3. In some embodiments of any of the aspects, the IL is at a concentration of at least 25% w / w and has a ratio of catiomanion of 1:3 or 1:4. In some embodiments of any of the aspects, the IL is at a concentration of at least 25% w / w in water and has a ratio of catiomanion of 1:3 or 1 :4. In some embodiments of any of the aspects, the IL is a gel, or a shear -thining Newtonian gel.

[0163] In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from about 10: 1 to about 1: 10. In some embodiments of any of the aspects, the IL has a ratio of cation: anion of from 10: 1 to 1: 10. In some embodiments of any of the aspects, the IL has a ratio of cation: anion of from about 5:1 to about 1:5. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from 5: 1 to 1 :5. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from about 2: 1 to about 1:4. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from 2: 1 to 1 :4. In some embodiments of any of the aspects, the IL has a ratio of cation: anion of from about 2: 1 to about 1: 10. hr some embodiments of any of the aspects, the IL has a ratio of cation: anion of from about 2: 1 to about 1 : 1. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from about 2: 1 to about 1 :2.

[0164] In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from 2: 1 to 1 : 10. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from 2: 1 to 1: 1. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from 2: 1 to 1:2.

[0165] In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from about 2.5:1 to about 1:2.5. hr some embodiments of any of the aspects, the IL has a ratio of catiomanion of from 2.5 : 1 to 1 :2.5. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from about 3:1 to about 1:3. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from 3:1 to 1 :3. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from about 4: 1 to about 1:4. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from 4: 1 to 1 :4.

[0166] In some embodiments of any of the aspects, the IL has a ratio of catiomanion such that there is a greater amount of anion, e.g., a ratio of less than 1: 1. In some embodiments of any of the aspects, the IL has a ratio of catiomanion such that there is an excess of anion. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from about 1: 1 to about 1 : 10. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from 1 : 1 to 1 : 10. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from about 1 : 1 to about 1 :4. In some embodiments of any of tire aspects, the IL has a ratio of catiomanion of from 1 : 1 to 1 :4. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from about 1 : 1 to about 1 :3. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from 1 : 1 to 1:3. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from about 1 : 1 to about 1 :2. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of from 1 : 1 to 1 :2. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of about 1 : 1, 1:2, 1 :3, or 1 :4. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of 1: 1, 1:2, 1 :3, or 1 :4. In some embodiments of any of the aspects, the IL has a ratio of catiomanion less than about of 1 : 1. In some embodiments of any of the aspects, the IL has a ratio of catiomanion less than 1: 1. Without wishing to be constrained by theory, compositions with higher amounts of anion relative to cation display greater hydrophobicity.

[0167] In some embodiments of any of the aspects, the IL has a catiomanion ratio with an excess of cation. In some embodiments of any of the aspects, the IL has a catiomanion ratio of 1: 1 or less anion.

[0168] In some embodiments of any of the aspects, e.g., when one or more nucleic acid molecules are provided in combination with the IL, the ratio of catiomanion is greater than 1: 1, e.g., greater than 1 :2, from about 1:2 to about 1 :4, or from 1:2 to 1 :4.

[0169] In some embodiments of any of the aspects, the IL has a ratio of catiomanion of about 2: 1. In some embodiments of any of the aspects, the IL has a ratio of catiomanion about of 1 : 1. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of 2: 1. In some embodiments of any of the aspects, the IL has a ratio of catiomanion of 1 : 1.

[0170] In some embodiments of any of the aspects, the IL has a ratio of catiomanion of 1 : 1 j^l%. In some embodiments of any of tire aspects, the IL has a ratio of catiomanion of 1: 1 +_2%. In someembodiments of any of the aspects, the IL has a ratio of cation:anion of 1:1 ±_5%. In some embodiments of any of the aspects, the IL has a ratio of cation :anion of 1:1 j^lO%.

[0171] In some embodiments of any of the aspects, the IL has a ratio of cation:anion of 2:1 4M%. In some embodiments of any of tire aspects, the IL has a ratio of cation:anion of 2: 1 + 2%. In some embodiments of any of the aspects, the IL has a ratio of cation:anion of 2:1 ±_5%. In some embodiments of any of the aspects, the IL has a ratio of cation:anion of 2:1 4^10%.

[0172] In some embodiments of any of the aspects, the IL has a ratio of cation:anion of 1:2 4^1%. In some embodiments of any of the aspects, the IL has a ratio of cation:anion of 1:2 +_2%. In some embodiments of any of the aspects, the IL has a ratio of cation:anion of 1:2 ±_5%. In some embodiments of any of the aspects, the IL has a ratio of cation:anion of 1:2 4^10%.

[0173] In some embodiments of any of the aspects, the IL is at a concentration of at least 20 mM. In some embodiments of any of tire aspects, the IL is at a concentration of at least about 20 mM. In some embodiments of any of the aspects, the IL is at a concentration of at least 25 mM. In some embodiments of any of the aspects, the IL is at a concentration of at least about 25 mM. In some embodiments of any of the aspects, the IL is at a concentration of at least 50 mM. In some embodiments of any of the aspects, the IL is at a concentration of at least about 50 mM. In some embodiments of any of the aspects, the IL is at a concentration of at least 100 mM. 500 mM, 1 M, 2 M, 3 M or greater. In some embodiments of any of the aspects, the IL is at a concentration of at least about 100 mM, 500 mM, 1 M, 2 M, 3 M or greater.

[0174] In some embodiments of any of the aspects, the IL is at a concentration of from about 50 mM to about 4 M. In some embodiments of any of the aspects, the IL is at a concentration of from 50 mM to 4 M. In some embodiments of any of the aspects, the IL is at a concentration of from about 500 mM to about 4 M. In some embodiments of any of the aspects, the IL is at a concentration of from 500 mM to 4 M. In some embodiments of any of the aspects, the IL is at a concentration of from about 1 M to about 4 M. In some embodiments of any of the aspects, the IL is at a concentration of from 1 M to 4 M. In some embodiments of any of the aspects, the IL is at a concentration of from about 2 M to about 4 M. In some embodiments of any of the aspects, the IL is at a concentration of from 2 M to 4 M.

[0175] In some embodiments of any of the aspects, the IL concentration in the composition or formulation is about 0.1 mM to 20 mM. In some embodiments of any of the aspects, the IL concentration in the composition or formulation is about 0.5 mM to 20 mM, 0.5 mM to 18 mM, 0.5 mM to 16 mM, 0.5 mM to 14 mM, 0.5 mM to 12 mM. 0.5 mM to 10 mM, 0.5 mM to 8 mM. 1 mM to 20 mM, 1 mM to 18 mM, 1 mM to 16 mM, 1 mM to 14 mM, ImM to 12 mM, 1 mM to 10 mM, 1 mM to 8 mM, 2 mM to 20 mM, 2 mM to 18 mM, 2 mM to 16 mM. 2 mM to 14 mM, 2 mM to 12 mM, 2 mM to 10 mM. 2 mM to 8 mM, 4 mM to 20 mM. 4 mM to 18 mM, 4 mM to 16 mM. 4 mM to 14 mM. 4 mM to 12 mM, 4 mM to 10 mM, 4 mM to 8 mM, 6 mM to 20 mM. 6 mM to 18 mM, 6mM to 14 mM, 6 mM to 12 mM, 6 mM to 10 mM, 6 mM to 8 mM, 8 mM to 20 mM, 8 mM to 18 mM, 8 mM to 16 mM, 8 mM to 14 mM, 8 mM to 12 mM, 8 mM to 10 mM, 10 mM to 20 mM, 10 mM to 18 mM, 10 mM to 16 mM, 10 mM to 14 mM, 10 mM to 12 mM, 12 mM to 20 mM, 12 mM to 18 mM, 12 mM to 16 mM, 12 mM to 14 mM, 14 mM to 20 mM, 14 mM to 18 mM, 14 mM to 16 mM, 16 mM to 20 mM, 16 mM to 18 mM, orl8 mM to 20 mM. In some embodiments of any of the aspects, the IL concentration in the composition or formulation is about ImM, about 2 mM, about 3mM. about 4mM, about 5 mM, about 6 mM, about 7 mM, about 8 mM, about 9 mM. about 10 mM, about 11 mM, about 12 mM, about 13 mM, about 14 mM, about 15 mM, about 16 mM, about 17 mM, about 18 mM, about 19 mM or about 20 mM.

[0176] In some embodiments of any of the aspects, the composition comprises at least one ionic liquid and further comprises at least a second ionic liquid. In some embodiments of any of the aspects, the composition comprises a first ionic liquid and further comprises at least a second ionic liquid. Combinations of two, three, four, five, or more of any of the ionic liquids described herein are contemplated.

[0177] In some embodiments of any of the aspects wherein the composition comprises two or more ionic liquids, a first and second ionic liquid have the same cation, e.g.. acetylcholine. In some embodiments of any of the aspects wherein the composition comprises tw o or more ionic liquids, a first and second ionic liquid have different anions.

[0178] In some embodiments of any of the aspects wherein the composition comprises tw o or more ionic liquids, the second ionic liquid is choline and geranic acid (CAGE).

[0179] It is specifically contemplated that a composition or combination described herein can comprise one, two. three, or more of any of the types of components described herein. For example, a composition can comprise a mixture, solution, combination, or emulsion of two or more different ionic liquids (e.g., different ionic liquids described herein), and / or a mixture, solution, combination, or emulsion of tw o or more different non-ionic surfactants, and / or a mixture, solution, combination, or emulsion of tw o or more different active compounds.

[0180] In some embodiments of any of the aspects, the one or more ILs can be in combination with at least one compound, e.g., a further compound, active compound, or cargo molecule. As used herein, “in combination with” refers to two or more substances being present in the same formulation in any molecular or physical arrangement, e.g., in an admixture, in a solution, in a mixture, in a suspension, in a colloid, in an emulsion. The formulation can be a homogeneous or heterogenous mixture. In some embodiments of any of the aspects, the active compound(s) can be comprised by a superstructure, e.g., nanoparticles, liposomes, vectors, cells, scaffolds, or the like, said superstructure is which in solution, mixture, admixture, suspension, etc., with the IL. In some embodiments of any of the aspects, the at least one IL as described herein is in combination with at least one activecompound. In some embodiments of any of the aspects, an IL as described herein is in combination with at least one active compound.

[0181] As used herein, an “active compound” or “active agent” is any agent which will exert an effect on a target cell or organism. The terms “compound” and “agent” refer to any entity which is normally not present or not present at the levels being administered and / or provided to a cell, tissue or subject. An agent can be selected from a group comprising: chemicals; small organic or inorganic molecules; signaling molecules; nucleic acid sequences; nucleic acid analogues: proteins; peptides: enzymes; aptamers; peptidomimetic, peptide derivative, peptide analogs, antibodies; intrabodies: biological macromolecules, extracts made from biological materials such as bacteria, plants, fungi, or animal cells or tissues: naturally occurring or synthetic compositions or functional fragments thereof. In some embodiments, the agent is any chemical, entity or moiety, including without limitation synthetic and naturally -occurring non-proteinaceous entities. Agents can be known to have a desired activity and / or property, or can be selected from a library of diverse compounds. Non-limiting examples of active compounds contemplated for use in the methods described herein include small molecules, polypeptides, nucleic acids, chemotherapies / chemotherapeutic compounds, antibodies, antibody reagents, vaccines, a GLP-1 polypeptide or mimetic / analog thereof, insulin, acarbose. rituximab, or ruxolitinib. An active compound may also be referred to herein as a “cargo molecule.”

[0182] A nucleic acid molecule, as described herein, can be a vector, an expression vector, an inhibitory nucleic acid, an aptamer, a template molecule or cassette (e.g., for gene editing), or a targeting molecule (e.g., for CRISPR-Cas technologies), or any other nucleic acid molecule that one wishes to deliver to a cell. The nucleic acid molecule can be RNA. DNA, or synthetic or modified versions thereof. In some embodiments of any of the aspects, the nucleic acid is an inhibitory nucleic acid, e.g., a siRNA. In some embodiments of any of the aspects, the nucleic acid is a siRNA, pDNA, or mRNA. In some embodiments of any of the aspects, the nucleic acid is a robed nucleic acid.

[0183] In one aspect of any of the embodiments, described herein is a method of delivering a nucleic acid molecule to a cell, the method comprising contacting the cell with the nucleic acid molecule in combination with one or more ILs as described herein. In some embodiments of any of the aspects, the cell is a cell in a subject and the contacting step comprises administering the nucleic acid molecule in combination with the one or more ILs to the subject. In some embodiments of any of the aspects, the cell is in vitro, in vivo, or ex vivo. In some embodiments of any of the aspects, the cell is eukaryotic. In some embodiments of any of the aspects, the cell is mammalian. In some embodiments of any of the aspects, the cell is an epithelial cell, e.g., an intestinal epithelial cell. In some embodiments of any of the aspects the cell is an epidermal cell.

[0184] As used herein, the term “small molecule” refers to a chemical agent which can include, but is not limited to, a peptide, a peptidomimetic, an amino acid, an amino acid analog, a polynucleotide, a polynucleotide analog, an aptamer, a nucleotide, a nucleotide analog, an organic orinorganic compound (i.c., including hctcroorganic and organometallic compounds) having a molecular weight less than about 10,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 5,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 1,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 500 grams per mole, and salts, esters, and other pharmaceutically acceptable fonns of such compounds.

[0185] In some embodiments of any of the aspects, the active compound can be a therapeutic compound or drug, e.g., an agent or compound which is therapeutically effective for the treatment of at least one condition in a subject. Therapeutic compounds are known in the art for a variety of conditions, see, e.g., the database available on the world wide web at drugs.com or the catalog of FDA-approved compounds available on the world wide web at catalog.data.gov / dataset / drugsf da- database; each of which is incorporated by reference herein in its entirety.

[0186] By way of non-limiting example, exemplary antibodies and / or antibody reagents suitable for use as active compounds / therapeutic compounds herein include: abeiximab; adalimumab; adlimumab-atto; ado-trastuzumab; ado-trastuzumab emtansine; alemtuzumab; alirocumab; atezolizumab; avelumab; basiliximab; belimumab; bevacizumab; bezlotoxumab; blinatumomab; brentuximab; brentuximab vedotin; brodalumab; canakinumab; capromab; capromab pendetide; certolizumab; certolizumab pegol; cetuximab; daclizumab; daratumumab; denosumab; dinutuximab; dupilumab; durvalumab; eculizumab; elotuzumab; evolocumab; etanercept; etanercept-szzs; golimumab; ibritumomab; ibritumomab tiuxetan; idarucizumab; infliximab; infliximab-abda; infliximab-dyyb; ipilimumab; ixekizumab; mepolizumab; natalizumab; necitumumab; nivolumab; obiltoxaximab; obinutuzumab; ocrelizumab; ofatumumab; olaratumab; omalizumab; palivizumab; panitumumab; pembrolizumab; pertuzumab; ramucriumab; ranibizumab; raxibacumab; reslizumab; rituximab; secukinumab; siltuximab; tocilizumab; trastuzumab; ustekinumab; vedolizumab; sarilumab; guselkumab; inotuzumab ozogamicin; inotuzumab; adalimumab-adbm, gemtuzumab ozogamicin; gemtuzumab; bevacizumab-awwb; benralizumab; emicizumab; emicizumab-kxwh; trastuzumab-dkst; infliximab-qbtx; ibalizumab: ibalizumab-uiyk; tildrakizumab; tildrakizumab-asmn; burosumab; burosumab-twza; erenumab; erenumab-aooe; tositumomab; mogamulizumab; moxetumomab; moxetumomab pasudotox; cemiplimab; polatuzumab; catumaxomab; polatuzumab vedotin; and combinations thereof, including bispecific antibodies made by combining portions of the foregoing.

[0187] By way of non-limiting example, exemplary inhibitory nucleic acids suitable for use as active compounds / therapeutic compounds herein include: patisiran; and combinations thereof, including bispecific antibodies made by combining portions of the foregoing.

[0188] As used herein the term "chemotherapeutic agent" refers to any chemical or biological agent with therapeutic usefulness in the treatment of diseases characterized by abnormal cell growth.Such diseases include tumors, neoplasms and cancer as well as diseases characterized by hyperplastic growth. These agents can function to inhibit a cellular activity upon which the cancer cell depends for continued proliferation. In some aspect of all tire embodiments, a chemotherapeutic agent is a cell cycle inhibitor or a cell division inhibitor. Categories of chemotherapeutic agents that are useful in the methods of the invention include alkylating / alkaloid agents, antimetabolites, hormones or hormone analogs, and miscellaneous antineoplastic drugs. Most of these agents are directly or indirectly toxic to cancer cells. In one embodiment, a chemotherapeutic agent is a radioactive molecule.

[0189] In some embodiments of any of the aspects, the active compound is a hydrophobic molecule, e.g., estradiol, testosterone, corticosterone, paclitaxel, doxorubicin, cisplatin, and / or camptothecin. In some embodiments of any of the aspects, the active compound is a hydrophilic molecule.

[0190] In some embodiments of any of the aspects, the active compound is a polypeptide. In some embodiments of any of the aspects, the active compound is an antibody or antibody reagent. As used herein, the term “antibody reagent" refers to a polypeptide that includes at least one immunoglobulin variable domain or immunoglobulin variable domain sequence and which specifically binds a given antigen. An antibody reagent can comprise an antibody or a polypeptide comprising an antigen-binding domain of an antibody. In some embodiments, an antibody reagent can comprise a monoclonal antibody or a polypeptide comprising an antigen-binding domain of a monoclonal antibody. For example, an antibody can include a heavy (H) chain variable region (abbreviated herein as VH), and a light (L) chain variable region (abbreviated herein as VL). In another example, an antibody includes two heavy (H) chain variable regions and two light (L) chain variable regions. The term "antibody reagent" encompasses antigen-binding fragments of antibodies (e.g., single chain antibodies, Fab and sFab fragments, F(ab')2, Fd fragments, Fv fragments, scFv, and domain antibodies (dAb) fragments as well as complete antibodies.

[0191] In some embodiments of any of the aspects, the active compound has a molecular weight of greater than about 450. In some embodiments of any of die aspects, the active compound has a molecular weight of greater than about 500. In some embodiments of any of the aspects, the active compound has a molecular weight of greater than 450, e.g., greater than 450, greater than 500, greater than 550, greater than 600, greater than 1000 or more. In some embodiments of any of the aspects, the active compound is polar.

[0192] In some embodiments, the inhibitory nucleic acid is a NFKBIZ inhibitory nucleic acid, e.g., it binds to a NFKBIZ mRNA and inhibits the expression of NFKBIZ. As used herein, “NFKBIZ” or “NFKB inhibitor zeta” refers to an inhibitor of nuclear factor KB (IKB) protein IKBL that plays a key role in the regulation of NF-KB complexes. It is a direct transcription activator of TNF-a-. IL-17A-, and IL-36-inducible psoriasis-related gene products that are involved ininflammatory signaling, neutrophil chemotaxis, and leukocyte activation. Accordingly, provided herein are methods of treating psoriasis, e.g., by administering a composition described herein comprising an active agent that is an inhibitor of NFKBIZ, e.g., a NFKBIZ inhibitory nucleic acid. Sequences of NFKBIZ from a number of species are known in the art, e.g., human NFKBIZ sequences are available in the NCBI database under the 64332 Gene ID (e.g., mRNAs NM 001005474.3 (SEQ ID NO: 5) andNM_031419.4 (SEQ ID NO: 6)). One of skill in the art can readily design an NFKBIZ inhibitory nucleic acid, e.g., using an automated tool as described above herein. NKFBIZ inhibitory nucleic acids are also commercially available, e.g., catalog no. J-040680- 06-0050 from Dharmacon (Lafayette. CO).

[0193] In some embodiments, the inhibitory nucleic acid is a TNF-alpha inhibitory nucleic acid, e.g., it binds to a TNF-alpha mRNA and inhibits the expression of TNF-alpha. As used herein, “tumor necrosis factor alpha” or “TNF-alpha” refers to a pro-inflammatory cytokine implicated in autoimmune disease, psoriasis, and other conditions. Accordingly, provided herein are methods of treating inflammatory conditions (e.g., psoriasis) and / or reducing or inhibition inflammation, e.g., by administering a composition described herein comprising an active agent that is an inhibitor of TNF- alpha, e.g.. a TNF-alpha inhibitory nucleic acid. Sequences of TNF-alpha from a number of species are known in the art, e.g.. human TNF-alpha sequences are available in the NCBI database under the 7124 Gene ID (e.g., mRNA NM 000594.4 (SEQ ID NO: 7)). One of skill in the art can readily design a TNF-alpha inhibitory nucleic acid, e.g., using an automated tool as described above herein. TNF- alpha inhibitory nucleic acids are also commercially available, e.g., catalog nos. J-010546-09-0002. J- 010546-10-0002, J-010546-11-0002, and J-010546-12-0002, from Dharmacon (Lafayette, CO).

[0194] In some embodiments, the inhibitory nucleic acid is an IL- 17 inhibitor}’ nucleic acid, e.g., it binds to an IL- 17 mRNA and inhibits the expression of IL- 17. As used herein, “interleukin 17” or “IL-17” refers to a pro-inflammatory cytokine produced by activating T cells implicated in autoimmune disease, psoriasis, rheumatoid arthritis, multiple sclerosis, and other conditions. Accordingly, provided herein are methods of treating inflammatory conditions (e.g., psoriasis) and / or reducing or inhibition inflammation, e.g., by administering a composition described herein comprising an active agent that is an inhibitor of IL-17, e.g., an IL-17 inhibitory nucleic acid. Sequences of IL-17 from a number of species are known in the art, e.g., human IL-17 sequences are available in the NCBI database under the 3605 Gene ID (e.g., mRNANM_002190.3 (SEQ ID NO: 8)). One of skill in the art can readily design an IL-17 inhibitory nucleic acid, e.g., using an automated tool as described above herein. IL-17 inhibitory nucleic acids are also commercially available, e.g., catalog no. J- 007937-05-0002, J-007937-06-0002, J-007937-07-0002. and J-007937-08-0002 from Dharmacon (Lafayette, CO).

[0195] In one aspect of any of the embodiments, provided herein is a method of treating an inflammatory condition and / or a method of reducing inflammation in a subject in need thereof, the method comprising administering a composition described herein, comprising at least one IL and at least one anti-inflammatory agent to the subject. In some embodiments of any of the aspects, the antiinflammatory agent is an inhibitor}' nucleic acid that targets one or more pro-inflammatory gene products, e.g., IL-17, TNF-alpha, and / or NFKBIZ.

[0196] As used herein, “inflammation" refers to the complex biological response to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Accordingly, the term “inflammation" includes any cellular process that leads to the production of pro-inflammatory cytokines, inflammation mediators and / or the related downstream cellular events resulting from the actions of the cytokines thus produced, for example, fever, fluid accumulation, swelling, abscess formation, and cell death. Inflammation can include both acute responses (i.e., responses in which the inflammatory processes are active) and chronic responses (i.e., responses marked by slow progression and formation of new connective tissue). Acute and chronic inflammation may be distinguished by the cell types involved. Acute inflammation often involves polymorphonuclear neutrophils; whereas chronic inflammation is normally characterized by a lymphohistiocytic and / or granulomatous response.

[0197] An inflammatory condition is any disease state characterized by inflammatory tissues (for example, infiltrates of leukocytes such as lymphocytes, neutrophils, macrophages, eosinophils, mast cells, basophils and dendritic cells) or inflammatory processes which provoke or contribute to the abnormal clinical and histological characteristics of the disease state. Inflammatory conditions include, but are not limited to. inflammatory' conditions of the skin, inflammatory conditions of the lung, inflammatory conditions of the joints, inflammatory conditions of the gut, inflammatory conditions of the eye. inflammatory conditions of the endocrine system, inflammatory conditions of the cardiovascular system, inflammatory conditions of the kidneys, inflammatory conditions of the liver, inflammatory conditions of the central nervous system, or sepsis-associated conditions. In some embodiments, the inflammatory condition is associated with wound healing. In some embodiments,the inflammation to be treated according to the methods described herein can be skin inflammation; inflammation caused by substance abuse or drug addiction; inflammation associated with infection; inflammation of the cornea; inflammation of the retina; inflammation of the spinal cord; inflammation associated with organ regeneration; and pulmonary inflammation.

[0198] In some embodiments, the inflammatory condition is an inflammatory condition of the skin. In some embodiments of the aspects, the inflammatory condition is an autoimmune disease.

[0199] Non-limiting examples of inflammatory conditions of the skin can include psoriasis, such as Sweet's syndrome, pyodenna gangrenosum, subcorneal pustular dermatosis, erythema elevatum diutinum, Behcet's disease or acute generalized exanthematous pustulosis, a bullous disorder, psoriasis, a condition resulting in pustular lesions, acne, acne vulgaris, dermatitis (e.g. contact dermatitis, atopic dermatitis, seborrheic dermatitis, eczematous dermatitides, eczema craquelee, photoallergic dermatitis, phototoxicdermatitis, phytophotodermatitis, radiation dermatitis, stasis dermatitis or allergic contact dermatitis), eczema, ulcers and erosions resulting from trauma, bums, ischemia of the skin or mucous membranes, several forms of ichthyoses, epidermolysis bullosae, hypertrophic scars, keloids, cutaneous changes of intrinsic aging, photoaging, frictional blistering caused by mechanical shearing of the skin, cutaneous atrophy resulting from the topical use of corticosteroids, and inflammation of mucous membranes (e g., cheilitis, chapped lips, nasal irritation, mucositis and vulvovaginitis).

[0200] In some embodiments, an inflammatory condition can be an autoimmune disease. Nonlimiting examples of autoimmune diseases can include: Type 1 diabetes; systemic lupus erythematosus; rheumatoid arthritis; psoriasis; inflammatory^ bowel disease; Crohn’s disease; and autoimmune thyroiditis.

[0201] By way of non-limiting example, inflammatory conditions can be inflammatory conditions of the lung, such as asthma, bronchitis, chronic bronchitis, bronchiolitis, pneumonia, sinusitis, emphy sema, adult respiratory distress sy ndrome, pulmonary inflammation, pulmonary’ fibrosis, and cystic fibrosis (which may additionally or alternatively involve the gastro-intestinal tract or other tissue(s)). By way of non-limiting example, inflammatory conditions can be inflammatory conditions of the joints, such as rheumatoid arthritis, rheumatoid spondylitis, juvenile rheumatoid arthritis, osteoarthritis, gouty arthritis, infectious arthritis, psoriatic arthritis, and other arthritic conditions. By way of non-limiting example, inflammatory conditions can be inflammatory conditions of the gut or bowel, such as inflammatory bowel disease, Crohn's disease, ulcerative colitis and distal proctitis. By way of non-limiting example, inflammatory conditions can be inflammatory conditions of the eye, such as dry eye syndrome, uveitis (including iritis), conjunctivitis, scleritis. and keratoconjunctivitis sicca. By way of non-limiting example, inflammatory’ conditions can be inflammatory conditions of the endocrine system, such as autoimmune thyroiditis (Hashimoto's disease), Graves’ disease, Type I diabetes, and acute and chronic inflammation of the adrenal cortex.By way of non-limiting example, inflammatory conditions can be inflammatory conditions of the cardiovascular system, such as coronary infarct damage, peripheral vascular disease, myocarditis, vasculitis, revascularization of stenosis, atherosclerosis, and vascular disease associated with Type II diabetes. By way of non-limiting example, inflammatory conditions can be inflammatory conditions of the kidneys, such as glomerulonephritis, interstitial nephritis, lupus nephritis, and nephritis secondary to Wegener's disease, acute renal failure secondary to acute nephritis, post-obstructive syndrome and tubular ischemia. By way of non-limiting example, inflammatory conditions can be inflammatory conditions of the liver, such as hepatitis (arising from viral infection, autoimmune responses, drug treatments, toxins, environmental agents, or as a secondary consequence of a pri ary disorder), biliary atresia, primary biliary cirrhosis and primary sclerosing cholangitis. By way of nonlimiting example, inflammatory conditions can be inflammatory conditions of the central nervous system, such as multiple sclerosis and neurodegenerative diseases such as Alzheimer's disease or dementia associated with HIV infection. By way of non-limiting example, inflammatory conditions can be inflammatory conditions of the central nervous system, such as MS; all types of encephalitis and meningitis; acute disseminated encephalomyelitis; acute transverse myelitis; neuromyelitis optica; focal demyelinating syndromes (e.g., Balo's concentric sclerosis and Marburg variant of MS); progressive multifocal leukoencephalopathy; subacute sclerosing panencephalitis; acute haemorrhagic leucoencephalitis (Hurst's disease); human T-lymphotropic virus type- 1 associated myelopathy / tropical spactic paraparesis; Devic's disease; human immunodeficiency virus encephalopathy; human immunodeficiency virus vacuolar myelopathy; peripheral neuropathies; Guillain-Barre Syndrome and other immune mediated neuropathies; and myasthenia gravis. By way of non-limiting example, inflammatory conditions can be sepsis-associated conditions, such as systemic inflammatory response syndrome (SIRS), septic shock or multiple organ dysfunction syndrome (MODS). Further non-limiting examples of inflammatory conditions include, endotoxin shock, periodontal disease, polychondritis; periarticular disorders; pancreatitis; system lupus erythematosus; Sjogren's syndrome; vasculitis sarcoidosis amy loidosis; allergies; anaphylaxis; systemic mastocytosis; pelvic inflammatory disease; multiple sclerosis; multiple sclerosis (MS); celiac disease, Guillain-Barre syndrome, sclerosing cholangitis, autoimmune hepatitis, Raynaud's phenomenon, Goodpasture's syndrome, Wegener's granulomatosis, polymyalgia rheumatica, temporal arteritis / giant cell arteritis, chronic fatigue syndrome CFS), autoimmune Addison's Disease, ankylosing spondylitis, Acute disseminated encephalomyelitis, antiphospholipid antibody syndrome, aplastic anemia, idiopathic thrombocytopenic purpura. Myasthenia gravis, opsoclonus myoclonus syndrome, optic neuritis. Ord's thyroiditis, pemphigus, pernicious anaemia, polyarthritis in dogs, Reiter's syndrome. Takayasu's arteritis, warm autoimmune hemolytic anemia, fibromyalgia (FM), autoinflammatory PAPA syndrome, Familial Mediterranean Fever, polymyalgia rheumatica. polyarteritis nodosa, churg strauss syndrome; fibrosing alveolitis, hypersensitivity pneumonitis,allergic aspergillosis, cryptogenic pulmonary’ eosinophilia, bronchiolitis obliterans organising pneumonia; urticaria; lupoid hepatitis; familial cold autoinflammatory syndrome, Muckle-Wells syndrome, the neonatal onset multisystem inflammatory disease, graft rejection (including allograft rejection and graft-v-host disease), otitis, chronic obstructive pulmonary’ disease, sinusitis, chronic prostatitis, reperfusion injury, silicosis, inflammatory my opathies, hypersensitivities and migraines. In some embodiments, an inflammatory condition is associated with an infection, e.g., viral, bacterial, fungal, parasite or prion infections. In some embodiments, an inflammatory condition is associated with an allergic response. In some embodiments, an inflammatory condition is associated with a pollutant (e.g.. asbestosis, silicosis, or berylliosis).

[0202] In some embodiments, the inflammatory' condition can be a local condition, e.g.. a rash or allergic reaction. In some embodiments, the inflammation is associated with a wound.

[0001] Anti-inflammatory agents are known in the art and can include, by way of non-limiting example, non-steroidal anti-inflammatory drugs (NSAIDs - such as aspirin, ibuprofen, or naproxen); corticosteroids, including glucocorticoids (e.g. cortisol, prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, triamcinolone, and beclometasone); methotrexate; sulfasalazine; leflunomide; anti-TNF medications; cyclophosphamide; pro-resolving drugs; my cophenolate; or opiates (e.g. endorphins, enkephalins, and dynorphin). steroids, analgesics, barbiturates, oxycodone, morphine, lidocaine, and inhibitors of pro-inflammatory gene products (e.g.. inhibitory nucleic acids as described above herein). Pro-inflammatory genes are known in the art and include, by way of non-limiting example, NKFBIZ, TNF-alpha, IL-17, IL-36 (IL-37alpha. IL-36beta, and IL-36gamma), IL-22, IL-17C, CXCL8, CCL20, IL23A, DEFB4, and LCN2.

[0002] In some embodiments of any of the aspects, the active compound is present at a concentration of at least about 100 mg / inL. In some embodiments of any of the aspects, the active compound is present at a concentration of at least about 150 mg / inL. In some embodiments of any of the aspects, the active compound is present at a concentration of at least about 200 mg / mL. In some embodiments of any of the aspects, the active compound is present at a concentration of at least about 250 mg / mL. In some embodiments of any of the aspects, the active compound is present at a concentration of at least about 300 mg / mL.

[0003] In some embodiments of any of the aspects, the active compound is present at a concentration of at least 100 mg / mL. In some embodiments of any of the aspects, the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the active compound is present at a concentration of at least 250 mg / mL. In some embodiments of any of the aspects, the active compound is present at a concentration of at least 300 mg / mL.

[0203] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in water and the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL.

[0204] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL.

[0205] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL.

[0206] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL.

[0207] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in water and the active compound is present at a concentration of at least 150 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL.

[0208] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in water and the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL.

[0209] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL.

[0210] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL.

[0211] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL.

[0212] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in water and the active compound is present at a concentration of at least 200 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL.

[0213] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 250 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in water and the active compound is present at a concentration of at least 250 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL.

[0214] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 250 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and the active compound is present at a concentration of at least 250 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL.

[0215] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 250 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 250 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL.

[0216] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 250 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 250 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL.

[0217] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 250 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in water and the active compound is present at a concentration of at least 250 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL.

[0218] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 300 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in water and the active compound is present at a concentration of at least 300 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL.

[0219] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 300 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and the active compound is present at a concentration of at least 300 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL.

[0220] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 300 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 300 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL.

[0221] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 300 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 300 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL.

[0222] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 300 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in water and the active compound is present at a concentration of at least 300 mg / mL. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL.

[0223] In some embodiments of any of the aspects, the composition has a viscosity of less than about 20 cP. In some embodiments of any of the aspects, the composition has a viscosity of less than 20 cP.

[0224] In some embodiments of any of the aspects, the composition has a viscosity of about 1 cP to about 20 cP. In some embodiments of any of the aspects, the composition has a viscosity of 1 cP to 20 cP.

[0225] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in water and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP.

[0226] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and tire active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP.

[0227] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 150 mg / mL and the composition hasa viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP.

[0228] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP.

[0229] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in water and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of less than 20 cP.

[0230] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in water and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP.

[0231] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatiblebuffer and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP.

[0232] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP.

[0233] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP.

[0234] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in water and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of less than 20 cP.

[0235] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in water and tire active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP.

[0236] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 250 mg / mL and the composition hasa viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP.

[0237] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP.

[0238] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP.

[0239] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in water and die active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of less than 20 cP.

[0240] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in water and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatiblebuffer and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP.

[0241] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP.

[0242] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP.

[0243] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP.

[0244] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in water and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of less than 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL.

[0245] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentrationof 1% to 30% v / v in water and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0246] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0247] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0248] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0249] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in water and the active compound is present at a concentration of at least 150 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the activecompound is present at a concentration of at least 150 mg / mL and the composition lias a viscosity of 1 cP to 20 cP.

[0250] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in water and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0251] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0252] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0253] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0254] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 200 mg / mL and the composition hasa viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, die IL is at a concentration of 1% to 5% v / v in water and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, tire IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 200 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0255] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in water and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0256] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0257] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, die IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0258] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible bufferand the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0259] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in water and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 250 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0260] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in water and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 30% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0261] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in water and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 20% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0262] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in water and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 15% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0263] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v and the active compound is present at a concentration of at least 300 mg / mL and the composition hasa viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, die IL is at a concentration of 1% to 10% v / v in water and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 10% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0264] In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in water and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP. In some embodiments of any of the aspects, the IL is at a concentration of 1% to 5% v / v in saline or a physiologically compatible buffer and the active compound is present at a concentration of at least 300 mg / mL and the composition has a viscosity of 1 cP to 20 cP.

[0265] As used herein, “composition” refers to any IL. combination of ILs, or combination of one or more ILs and one or more active agents described herein, unless further specified.

[0266] In some embodiments of any of the aspects, a composition or combination as described herein, comprising at least one IL and optionally an active compound can be formulated as an oral, subcutaneous, transdermal, intratumoral, intravenous, intradermal, or parenteral formulation. In some embodiments of any of the aspects, the composition or combination as described herein can be formulated for delivery' to a mucus membrane, e.g., to a nasal, oral, or vaginal membrane. In some embodiments of any of the aspects, an oral formulation can be a degradable capsule comprising the composition comprising the at least one IL and optionally, an active compound.

[0267] In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and optionally an active compound can be formulated as a subcutaneous, transdermal, or topical formulation. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a nucleic acid can be formulated as a subcutaneous, transdermal, or topical formulation. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a nucleic acid can be fonnulated as a subcutaneous formulation. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a nucleic acid can be formulated as a transdermal formulation.

[0268] In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a nucleic acid can be fonnulated as a subcutaneous, transdermal. or topical formulation for use in a method of treating a dermatological disease, e.g..psoriasis, basal cell carcinoma, squamous cell carcinoma, atopic dermatitis, alopecia, or aging. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and optionally an active compound can be formulated as a topical formulation. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a nucleic acid can be formulated as a topical formulation. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a nucleic acid can be formulated as a topical formulation for use in a method of treating a dermatological disease, e.g., psoriasis, basal cell carcinoma, squamous cell carcinoma, atopic dennatitis, alopecia, or aging.

[0269] In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a siRNA can be formulated as a subcutaneous, transdermal, or topical formulation. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a siRNA can be formulated as a subcutaneous, transdermal. or topical formulation for use in a method of treating a dermatological disease, e.g., psoriasis, basal cell carcinoma, squamous cell carcinoma, atopic dermatitis, alopecia, or aging. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a siRNA can be formulated as topical formulation. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a siRNA can be formulated as a topical formulation for use in a method of treating a dermatological disease, e.g., psoriasis, basal cell carcinoma, squamous cell carcinoma, atopic dennatitis. alopecia, or aging.

[0270] In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a pDNA can be formulated as a subcutaneous, transdermal, or topical formulation. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a pDNA can be formulated as a subcutaneous, transdermal, or topical formulation for use in a method of treating a dermatological disease, e.g., psoriasis, basal cell carcinoma, squamous cell carcinoma, atopic dennatitis, alopecia, or aging. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a pDNA can be fonnulated as a topical fonnulation. In some embodiments of any of the aspects, the composition or combination as described herein, comprising at least one IL and a pDNA can be formulated as a topical formulation for use in a method of treating a dermatological disease, e.g., psoriasis, basal cell carcinoma, squamous cell carcinoma, atopic dermatitis, alopecia, or aging.

[0271] In some embodiments of any of the aspects, described herein is a composition comprising at least one IL as described herein and at least one active compound. In some embodiments of any of the aspects, described herein is a composition consisting essentially of at least one IL as describedherein and at least one active compound. In some embodiments of any of the aspects, described herein is a composition consisting of at least one IL as described herein and at least one active compound. In some embodiments of any of the aspects, the composition comprising at least one IL as described herein and at least one active compound is administered as a monotherapy, e.g., another treatment for the condition is not administered to the subject.

[0272] In one aspect of any of the embodiments, described herein is a pharmacal composition comprising at least one active compound in combination with at least one IL as described herein. In some embodiments, the pharmacal composition comprises the at least one IL and the one or more active compounds as described herein. In some embodiments, the pharmacal composition consists essentially of the at least one IL and the one or more active compounds as described herein. In some embodiments, the pharmaceutical composition consists of the at least one IL and the one or more active compounds as described herein. In some embodiments, the pharmaceutical composition consists essentially of an aqueous solution of the at least one IL and the one or more active compounds as described herein. In some embodiments, the pharmaceutical composition consists of an aqueous solution of the at least one IL and the one or more active compounds as described herein.

[0273] The compositions, formulations, and combinations described herein can comprise at least one IL as described herein, e.g.. one IL, two ILs. three ILs, or more. In some embodiments of any of the aspects, a composition, formulation, or combination as described herein can comprise at least one IL as described herein and CAGE (Choline And GEranate).

[0274] In some embodiments of any of the aspects, the at least one active compound and the at least one ionic liquid are further in combination with at least one non-ionic surfactant. As used herein, “non-ionic surfactant” refers to a surfactant which lacks a net ionic charge and does not dissociate to an appreciable extent in aqueous media. The properties of non-ionic surfactants are largely dependent upon the proportions of the hydrophilic and hy drophobic groups in the molecule. Hydrophilic groups include the oxy ethy lene group (— OCH2 CH2 — ) and the hy droxy group. By varying the number of these groups in a hydrophobic molecule, such as a fatty' acid, substances are obtained which range from strongly hydrophobic and water insoluble compounds, such as glyceryl monostearate, to strongly hydrophilic and water-soluble compounds, such as the macrogols. Between these two extremes types include those in which the proportions of the hydrophilic and hydrophobic groups are more evenly balanced, such as the macrogol esters and ethers and sorbitan derivatives. Suitable non-ionic surfactants may be found in Martindale. The Extra Pharmacopoeia. 28th Edition, 1982, The Pharmaceutical Press, London, Great Britain, pp. 370 to 379. Non-limiting examples of non-ionic surfactants include polysorbates, a Tween™, block copolymers of ethylene oxide and propylene oxide, glycol and glycery l esters of fatty acids and their derivatives, polyoxyethylene esters of fatty acids (macrogol esters), polyoxyethylene ethers of fatty' acids and their derivatives (macrogolethers), polyvinyl alcohols, and sorbitan esters, sorbitan monocstcrs, ethers formed from fatty alcohols and polyethylene glycol, polyoxyethylene-polypropylene glycol, alkyl polyglycoside, Cetomacrogol 1000, cetostearyl alcohol, cetyl alcohol, cocamide DEA, cocamide MEA, decyl glucoside, decyl poly glucose, glycerol monostearate, IGEPAL CA-630, isoceteth-20, lauryl glucoside, maltosides, monolaurin, mycosubtilin, Nonidet P-40, nonoxynol-9, nonoxynols, NP-40. octaethylene glycol monododecyl ether, N-Octyl beta-D-thioglucopyranoside, octyl glucoside, oleyl alcohol. PEG-10 sunflower glycerides, pentaethylene glycol monododecyl ether, polidocanol, poloxamer. poloxamer 407, polyethoxylated tallow amine, poly glycerol polyricinoleate, sorbitan, sorbitan monolaurate, sorbitan monostearate, sorbitan tristearate, stearyl alcohol, surfactin, Triton X-100, and the like. In some embodiments of any of the aspects, the at least one non-ionic surfactant has a neutral hydrophilic head group.

[0275] As used herein, “polysorbate” refers to a surfactant derived from ethoxylated sorbitan (a derivative of sorbitol) esterified with fatty acids. Common brand names for polysorbates include Scathes™, Alkest™, Canarcel™, and Tween™. Exemplary polysorbates include polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate), polysorbate 40 (polyoxyethylene (20) sorbitan monopalmitate), polysorbate 60 (polyoxyethylene (20) sorbitan monostearate), and polysorbate 80 (polyoxyethylene (20) sorbitan monooleate).

[0276] In some embodiments of any of the aspects, the at least one non-ionic surfactant (e.g., at least one polysorbate) is present at a concentration of about 0.1% to about 50% w / v. In some embodiments of any of the aspects, the at least one non-ionic surfactant (e.g., at least one polysorbate) is present at a concentration of 0.1% to 50% w / v. In some embodiments of any of the aspects, the at least one non-ionic surfactant (e.g., at least one polysorbate) is present at a concentration of about 1% to about 5% w / v. In some embodiments of any of the aspects, the at least one non-ionic surfactant (e.g., at least one polysorbate) is present at a concentration of 1% to 5% w / v. In some embodiments of any of the aspects, the at least one non-ionic surfactant (e.g., at least one polysorbate) is present at a concentration of about 3% to about 10% w / v. In some embodiments of any of the aspects, the at least one non-ionic surfactant (e g., at least one polysorbate) is present at a concentration of 3% to 10% w / v. In some embodiments of any of the aspects, the at least one non-ionic surfactant (e.g., at least one polysorbate) is present at a concentration of less than about 5% w / v. In some embodiments of any of the aspects, the at least one non-ionic surfactant (e.g., at least one polysorbate) is present at a concentration of less than 5% w / v.

[0277] In some embodiments of any of the aspects, the combination of the at least one active compound and at least one IL as described herein is provided in one or more nanoparticles. In some embodiments of any of the aspects, the combination of the at least one active compound and at least one IL as described herein comprises nanoparticles comprising the active compound, thenanoparticlcs in solution or suspension in a composition comprising at least one IL as described herein.

[0278] In some embodiments of any of the aspects, a composition as described herein, e.g., a composition comprising at least one IL and an active compound, can further comprise a pharmaceutically acceptable carrier. As used herein, the terms "pharmaceutically acceptable", "physiologically tolerable" and grammatical variations thereof, as they refer to compositions, carriers, diluents and reagents, are used interchangeably and represent that the materials are capable of administration to or upon a mammal without the production of undesirable physiological effects such as nausea, dizziness, gastric upset and the like. A pharmaceutically acceptable carrier will not promote the raising of an immune response to an agent with which it is admixed, unless so desired. The preparation of a pharmacological composition that contains active ingredients dissolved or dispersed therein is well understood in the art and need not be limited based on formulation. Typically, such compositions are prepared as injectable either as liquid solutions or suspensions, however, solid forms suitable for solution, or suspensions, in liquid prior to use can also be prepared. The preparation can also be emulsified or presented as a liposome composition. The active ingredient can be mixed with excipients which are pharmaceutically acceptable and compatible with the active ingredient and in amounts suitable for use in the therapeutic methods described herein. Suitable excipients include, for example, water, saline, dextrose, glycerol, ethanol or the like and combinations thereof. In addition, if desired, the composition can contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents and the like which enhance the effectiveness of the active ingredient. The therapeutic composition of the present disclosure can include pharmaceutically acceptable salts of the components therein. Pharmaceutically acceptable salts include the acid addition salts (formed with the free amino groups of the polypeptide) that are formed with inorganic acids such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, tartaric, mandelic and the like. Salts formed with the free carboxyl groups can also be derived from inorganic bases such as, for example, sodium, potassium, ammonium, calcium or ferric hy droxides, and such organic bases as isopropylamine, trimethylamine, 2 -ethylamino ethanol, histidine, procaine and the like.Physiologically tolerable carriers are well known in the art. Exemplary liquid carriers are sterile aqueous solutions that contain no materials in addition to the active ingredients and water, or contain a buffer such as sodium phosphate at physiological pH value, phy siological saline or both, such as phosphate-buffered saline. Still further, aqueous carriers can contain more than one buffer salt, as well as salts such as sodium and potassium chlorides, dextrose, polyethylene glycol and other solutes. Liquid compositions can also contain liquid phases in addition to and to the exclusion of water. Exemplary of such additional liquid phases are glycerin, vegetable oils such as cottonseed oil, and water-oil emulsions. The amount of an active agent used in the methods described herein that will be effective in the treatment of a particular disorder or condition will depend on the nature of the disorderor condition, and can be determined by standard clinical techniques. Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, A. Osol, a standard reference text in this field of art. For example, a parenteral composition suitable for administration by injection is prepared by dissolving 1.5% by weight of active ingredient in 0.9% sodium chloride solution.

[0279] The term "carrier" in the context of a pharmaceutical carrier refers to a diluent, adjuvant, excipient, or vehicle with which the therapeutic is administered. Such pharmaceutical carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil. sesame oil and the like. Water is a preferred carrier when the pharmacal composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. These compositions can take the form of solutions, suspensions, emulsion, tablets, pills, capsules, powders, sustained- release formulations, and the like. The composition can be formulated as a suppository, with traditional binders and carriers such as triglycerides. Oral formulation can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Examples of suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, 18th Ed., Gennaro, ed. (Mack Publishing Co., 1990). The formulation should suit the mode of administration.

[0280] Pharmaceutically acceptable carriers and diluents include saline, aqueous buffer solutions, solvents and / or dispersion media. The use of such carriers and diluents is well known in the art. Some non-limiting examples of materials which can serve as pharmaceutically-acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, methy lcellulose, ethyl cellulose, microcry stalline cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) lubricating agents, such as magnesium stearate, sodium lauryl sulfate and talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, com oil and soybean oil; (10) glycols, such as propylene glycol;(11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol (PEG); (12) esters, such as ethyl oleate and ethyl laurate; (13) agar: (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) pH buffered solutions; (21) polyesters, polycarbonates and / or polyanhydrides; (22) bulking agents, such as polypeptides and amino acids (23) serum component, such as serum albumin, HDL and LDL; (22) C2-C12 alcohols, such as ethanol; and (23) other non-toxic compatible substances employed in pharmaceutical formulations. Wetting agents, coloring agents, release agents, coating agents, sweetening agents, flavoring agents, perfuming agents, preservative and antioxidants can also be present in the formulation. The terms such as "excipient", "carrier", "pharmaceutically acceptable carrier" or the like are used interchangeably herein. In some embodiments, the carrier inhibits the degradation of the active compound. The term "pharmaceutically acceptable carrier" excludes tissue culture medium.

[0281] In some embodiments of any of the aspects, a composition as described herein, e.g., a composition comprising at least one IL as described herein and an active compound, can be formulated as an oral, subcutaneous, intravenous, intradermal, or parenteral formulation. In some embodiments of any of the aspects, an oral formulation can be a degradable capsule comprising the composition described herein, e.g., a composition comprising at least one IL as described herein and an active compound.

[0282] In some embodiments of any of the aspects described herein, the biological activity of the active compound is improved or stabilized as compared to the activity in the absence of the at least one IL. In some embodiments of any of the aspects described herein, the IL greatly enhances permeation of the active compound across the skin compared to a control where the at least one IL is absent.

[0283] In one aspect of any of the embodiments, described herein is a method of administering at least active compound to a subject using a catheter wherein the catheter is coated with at least one IL as described herein. In one aspect of any of the embodiments, described herein is a method of collecting a body fluid by placing the catheter into the body wherein the catheter is coated with at least one IL as described herein.

[0284] In one aspect of any of the embodiments, the composition or combination described herein is for a method of stabilizing at least one active compound, e.g., at least one antibody. In one aspect of any of the embodiments, the composition or combination described herein is for a method of increasing the bioavailability of at least one active compound, e.g., at least one antibody. In one aspect of any of the embodiments, the composition or combination described herein is for a method of solubilizing at least one active compound, e.g., at least one antibody. In one aspect of any of the embodiments, the composition or combination described herein is for a method of providing a high concentration formulation of at least one active compound, e.g., at least one antibody. In one aspect of any of the embodiments, the composition or combination described herein is for a method of providing a high concentration formulation of at least one active compound, e.g., at least one antibody, at an injectable viscosity (e.g., less than 20 cP).

[0285] In one aspect of any of the embodiments, the composition or combination described herein is for a method of administering or delivering at least one active compound, e.g., for the treatment of a disease. In one aspect of any of the embodiments, described herein is a method ofadministering at least one active compound, the method comprising administering the active compound in combination with at least one IL as described herein. In one aspect of any of the embodiments, described herein is a method of treating a disease by administering at least one active compound, the method comprising administering the active compound in combination with at least one IL as described herein.

[0286] The disease treated by the methods described herein can be, e.g., cancer (breast cancer, leukemia, lymphoma, B-cell chronic lymphocytic leukemia, glioblastoma, carcinoma, urothelial carcinoma, lung cancer, colorectal cancer, lymphoblastic leukemia, lymphocytic leukemia, sarcoma, melanoma, prostate cancer, myeloma, multiple myeloma, Non-Hodgkin’s lymphoma), neuroblastoma, diabetes, an infection, inflammation, inflammatory diseases (e.g.. rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, crohn’s disease, ulcerative colitis, plaque psoriasis), autoimmune diseases, atopic dermatitis, gastrointestinal inflammation, inflammatory bowel disease (IBD). cholesterolemia. coronary artery disease, asthma, transplant / organ rejection, systemic lupus erythematosus, multiple sclerosis, osteoporosis, and the like.

[0287] In some embodiments, the methods described herein relate to treating a subject having or diagnosed as having a condition with a composition as described herein, e.g., a comprising at least one IL and an active compound. Subjects having a condition, e.g., diabetes, can be identified by a physician using current methods of diagnosing diabetes. Symptoms and / or complications of diabetes which characterize these conditions and aid in diagnosis are well known in the art and include but are not limited to, weight loss, slow healing, polyuria, polydipsia, polyphagiam headaches, itchy skin, and fatigue. Tests that may aid in a diagnosis of, e.g. diabetes include, but are not limited to, blood tests (e.g., for fasting glucose levels). A family history of diabetes, or exposure to risk factors for diabetes (e.g. overweight) can also aid in determining if a subject is likely to have diabetes or in making a diagnosis of diabetes.

[0288] The compositions and methods described herein can be administered to a subject having or diagnosed as having a condition described herein. In some embodiments, the methods described herein comprise administering an effective amount of compositions described herein, e.g. a composition comprising at least one IL as described herein and an active compound, to a subject in order to alleviate a symptom of a condition described herein. As used herein, "alleviating a symptom" is ameliorating any marker or symptom associated with a condition. As compared with an equivalent untreated control, such reduction is by at least 5%. 10%, 20%, 40%, 50%, 60%, 80%, 90%, 95%, 99% or more as measured by any standard technique. A variety of means for administering the compositions described herein to subjects are known to those of skill in the art. Such methods can include, but are not limited to oral, parenteral, intravenous, intramuscular, subcutaneous, transdermal, airway (aerosol), pulmonary, cutaneous, injection, or intratumoral administration. Administration can be local or systemic.

[0289] In some embodiments of any of the aspects, the administration is transdcrmal. In some embodiments of any of the aspects, the administration is transdermal, to a mucus membrane (e.g., to a nasal, oral, or vaginal membrane), oral, subcutaneous, intradermal, parenteral, intratumoral, or intravenous.

[0290] Oral administration can comprise providing tablets (including without limitation scored or coated tablets), pills, caplets, capsules, chewable tablets, powder packets, cachets, troches, wafers, aerosol sprays, or liquids, such as but not limited to, syrups, elixirs, solutions or suspensions in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion, or a water-in-oil emulsion. Oral formulations can comprise discrete dosage forms, such as, but not limited to, tablets (including without limitation scored or coated tablets), pills, caplets, capsules, chewable tablets, powder packets, cachets, troches, wafers, aerosol sprays, or liquids, such as but not limited to, syrups, elixirs, solutions or suspensions in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion, or a water-in-oil emulsion. Such compositions contain a predetermined amount of an IL and the at least one active compound, and may be prepared by methods of pharmacy well known to those skilled in the art. See generally. Remington: The Science and Practice of Pharmacy. 21st Ed., Lippincott. Williams, and Wilkins. Philadelphia PA. (2005).

[0291] In one aspect of any of the embodiments, described herein is a method of delivery of at least one active compound by subcutaneous, intradermal or intravenous administration, the method comprising administering the active compormd in combination with at least one IL as described herein. In some embodiments of any of the aspects, subcutaneous, intradermal or intravenous administration comprises administration via injection, catheter, port, or the like.

[0292] In one aspect of any of the embodiments, described herein is a method of parenteral delivery of at least one active compound, the method comprising parenterally administering the active compound in combination with at least one IL as described herein. In some embodiments, the parenteral administration comprises deliver}' to a tumor, e.g., a cancer tumor. In some embodiments of any of the aspects, the composition or combination described herein can be a parenteral dose form. Since administration of parenteral dosage forms typically bypasses the patient's natural defenses against contaminants, parenteral dosage forms are preferably sterile or capable of being sterilized prior to administration to a patient. Examples of parenteral dosage forms include, but are not limited to, solutions ready for injection, dry products ready to be dissolved or suspended in a pharmaceutically acceptable vehicle for injection, suspensions ready for injection, and emulsions. In addition, controlled-release parenteral dosage forms can be prepared for administration of a patient, including, but not limited to, DUROS®-type dosage forms and dose-dumping.

[0293] Suitable vehicles that can be used to provide parenteral dosage forms of a composition comprising at least one IL (e.g., CAGE) in combination with at least one active compound as disclosed within are well known to those skilled in the art. Examples include, without limitation:sterile water; water for injection USP; saline solution; glucose solution; aqueous vehicles such as but not limited to, sodium chloride injection, Ringer's injection, dextrose Injection, dextrose and sodium chloride injection, and lactated Ringer's injection; water-miscible vehicles such as, but not limited to, ethyl alcohol, polyethylene glycol, and propylene glycol; and non-aqueous vehicles such as, but not limited to. com oil, cottonseed oil, peanut oil, sesame oil, ethyl oleate, isopropyl myristate, and benzyl benzoate. Compounds that alter or modify the solubility of an ingredient in a composition as disclosed herein can also be incorporated into the parenteral dosage forms of the disclosure, including conventional and controlled-release parenteral dosage forms.

[0294] Conventional dosage forms generally provide rapid or immediate drug release from the formulation. Depending on the pharmacology and pharmacokinetics of the drug, use of conventional dosage forms can lead to wide fluctuations in the concentrations of the drug in a patient's blood and other tissues. These fluctuations can impact a number of parameters, such as dose frequency, onset of action, duration of efficacy, maintenance of therapeutic blood levels, toxicity, side effects, and the like. While as noted above herein, the compositions comprising the at least one IL in combination with at least one active compound can obviate certain reasons for using a controlled-release formulation, it is contemplated herein that the methods and compositions can be utilized in controlled- release formulations in some embodiments. For example, controlled-release formulations can be used to control a drug's onset of action, duration of action, plasma levels within the therapeutic window, and peak blood levels. In particular, controlled- or extended-release dosage forms or formulations can be used to ensure that the maximum effectiveness of a drug is achieved while minimizing potential adverse effects and safety concerns, which can occur both from under-dosing a drug (i.e., going below the minimum therapeutic levels) as well as exceeding the toxicity level for the drug. In some embodiments, the composition comprising the at least one IL in combination with at least one active compound can be administered in a sustained release formulation.

[0295] Controlled-release pharmaceutical products have a common goal of improving drug therapy over that achieved by their non-controlled release counterparts. Ideally, die use of an optimally designed controlled-release preparation in medical treatment is characterized by a minimum of drug substance being employed to cure or control the condition in a minimum amount of time. Advantages of controlled-release formulations include: 1) extended activity of die drug; 2) reduced dosage frequency; 3) increased patient compliance; 4) usage of less total drug; 5) reduction in local or systemic side effects; 6) minimization of drug accumulation; 7) reduction in blood level fluctuations; 8) improvement in efficacy of treatment; 9) reduction of potentiation or loss of drug activity; and 10) improvement in speed of control of diseases or conditions. Kim, Chemg-ju, Controlled Release Dosage Form Design, 2 (Technomic Publishing. Lancaster, Pa.: 2000).

[0296] Most controlled-release formulations are designed to initially release an amount of drug (active ingredient) that promptly produces the desired therapeutic effect, and gradually andcontinually release other amounts of drug to maintain this level of therapeutic or prophylactic effect over an extended period of time. In order to maintain this constant level of drug in the body, the drug must be released from the dosage form at a rate that will replace the amount of drug being metabolized and excreted from the body. Controlled-release of an active ingredient can be stimulated by various conditions including, but not limited to, pH, ionic strength, osmotic pressure, temperature, enzymes, water, and other physiological conditions or compounds.

[0297] A variety of known controlled- or extended-release dosage forms, formulations, and devices can be adapted for use with the salts and compositions of the disclosure. Examples include, but are not limited to. those described in U.S. Pat. Nos.: 3,845,770; 3,916,899; 3.536,809; 3,598,123; 4,008,719; 5674,533; 5,059,595; 5,591 ,767; 5,120,548; 5,073,543; 5.639.476; 5,354,556; 5,733,566; and 6.365,185 Bl; each of which is incorporated herein by reference. These dosage forms can be used to provide slow or controlled-release of one or more active ingredients using, for example, hydroxypropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems (such as OROS® (Alza Corporation, Mountain View, Calif. USA)), or a combination thereof to provide the desired release profile in varying proportions.

[0298] The term “effective amount" as used herein refers to the amount of a composition needed to alleviate at least one or more symptom of the disease or disorder, and relates to a sufficient amount of pharmacological composition to provide the desired effect. The term "therapeutically effective amount" therefore refers to an amount of a composition that is sufficient to provide a particular effect when administered to a typical subject. An effective amount as used herein, in various contexts, would also include an amount sufficient to delay the development of a symptom of the disease, alter the course of a symptom disease (for example but not limited to, slowing the progression of a symptom of the disease), or reverse a symptom of the disease. Thus, it is not generally practicable to specify an exact “effective amount". However, for any given case, an appropriate “effective amount" can be determined by one of ordinary skill in the art using only routine experimentation.

[0299] Effective amounts, toxicity , and therapeutic efficacy can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dosage can vary depending upon the dosage form employed and the route of administration utilized. The dose ratio between toxic and therapeutic effects is the therapeutic index and can be expressed as the ratio LD50 / ED50. Compositions and methods that exhibit large therapeutic indices are preferred. A therapeutically effective dose can be estimated initially from cell culture assays. Also, a dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the active compound, which achieves a half-maximal inhibition of symptoms) as determined in cell culture, or in an appropriate animal model. Levels in plasma can be measured, for example, by high performance liquidchromatography. The effects of any particular dosage can be monitored by a suitable bioassay, c.g., assay for blood glucose, among others. The dosage can be determined by a physician and adjusted, as necessary, to suit observed effects of the treatment.

[0300] As used herein, “diabetes” refers to diabetes mellitus, a metabolic disease characterized by a deficiency or absence of insulin secretion by the pancreas. As used throughout, "diabetes" includes Type 1. Type 2, Type 3, and Type 4 diabetes mellitus unless otherwise specified herein. The onset of diabetes is typically due to a combination of hereditary and environmental causes, resulting in abnormally high blood sugar levels (hyperglycemia). The two most common forms of diabetes are due to either a diminished production of insulin (in type 7). or diminished response by the body to insulin (in type 2 and gestational). Both lead to hyperglycemia, which largely causes the acute signs of diabetes: excessive urine production, resulting compensatory thirst and increased fluid intake, blurred vision, unexplained weight loss, lethargy, and changes in energy metabolism. Diabetes can cause many complications. Acute complications (hypoglycemia, ketoacidosis, or nonketotic hyperosmolar coma) may occur if the disease is not adequately controlled. Serious long-term complications (i.e. chronic side effects) include cardiovascular disease (doubled risk), chronic renal failure, retinal damage (which can lead to blindness), nerve damage (of several kinds), and microvascular damage, which may cause impotence and poor wound healing. Poor healing of wounds, particularly of the feet, can lead to gangrene, and possibly to amputation. In some embodiments, the diabetes can be Type 2 diabetes. Type 2 diabetes (non- insulin -dependent diabetes mellitus (NIDDM), or adult-onset diabetes) is a metabolic disorder that is primarily characterized by insulin resistance (diminished response by the body to insulin), relative insulin deficiency, and hyperglycemia. In some embodiments, a subject can be pre-diabetic, which can be characterized, for example, as having elevated fasting blood sugar or elevated post-prandial blood sugar.

[0301] Glucagon-Like Peptide-l(GLP-l), is known to reduce food intake and hunger feelings in humans and is an incretin derived from the transcription product of the proglucagon gene that contributes to glucose homeostasis. GLP-1 mimetics are currently being used in die treatment of Type 2 diabetes. Recent clinical trials have shown that these treatments not only improve glucose homeostasis but also succeed in inducing weight loss. As used herein. “GLP-1 polypeptide” refers to the various pre- and pro-peptides and cleavage products of GLP-1, c.g., for human: GLP-l(l-37) (SEQ ID NO: 2), GLP-1 (7-36) (SEQ ID NO: 3), and GLP-1 (7-37) (SEQ ID NO: 4). In some embodiments, a GLP-1 polypeptide can be GLP-1 (7-36) and / or GLP-1 (7-37) or the correlating polypeptides from a species other than human. Sequences for GLP-1 polypeptides are known in the art for a number of species, e.g. human GLP-1 (NCBI Gene ID: 2641) polypeptides (e.g., NCBI Ref Seq: NP 002045.1; SEQ ID NO: 1) and SEQ ID NOs: 2-4. In some embodiments, a pre or propeptide of GLP-1 can be used in the methods or compositions described herein, e.g.. a glucagon preproprotein (e.g., SEQ ID NO: 1). Naturally -occurring alleles or variants of any of the polypeptidesdescribed herein arc also specifically contemplated for use in the methods and compositions described herein.

[0302] SEQ ID NO: 11 mksiyfvagl fvmlvqgswq rslqdteeks rsfsasqadp Isdpdqmned krhsqgtfts 61 dyskyldsrr aqdfvqwlmn tkrnrnniak rhdeferhae gtftsdvssy legqaakefi 121 awlvkgrgrr dfpeevaive elgrrhadgs fsdemntild nlaardfmw liqtkitdrk

[0303] SEQ ID NO: 2 hdeferhae gtftsdvssy legqaakefi awlvkgrg

[0304] SEQ ID NO: 3 hae gtftsdvssy legqaakefi awlvkgr

[0305] SEQ ID NO: 4 hae gtftsdvssy legqaakefi awlvkgrg

[0306] Various GLP-1 mimetics are known in the art and used in the treatment of diabetes. GLP-1 mimetics (or analogues) can include exendin-4 (a Heloderma lizard polypeptide with homology to human GLP-1) and derivatives thereof, GLP-1 analogs modified to be DPP-IV resistant, or human GLP-1 polypeptides conjugated to various further agents, e.g., to extend the half-life. GLP- 1 mimetics / analogues can include, e.g., exenatide, lixisenatide, dulaglutide, semaglutide, albiglutide, LY2189265. liraglutide, and taspoglutide. Examples of such molecules and further discussion of their manufacture and activity can be found in the art. e.g., Gupta. Indian J. Endocrinol Metab 17:413-421 (2013); Garber. Diabetes Treatments 4LS279-S284 (2018); US Patent Publication US2009 / 0181912; and International Patent Publication WO2011 / 080103, each of which is incorporated by reference herein in its entirety.

[0307] In some embodiments of any of the aspects, the active compound can be a chemotherapeutic agent or agent effective for the treatment of cancer. As used herein, the term "cancer" relates generally to a class of diseases or conditions in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other comrective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

[0308] In some embodiments of any of the aspects, the cancer is a primary cancer. In some embodiments of any of the aspects, the cancer is a malignant cancer. As used herein, the term “malignant” refers to a cancer in which a group of tumor cells display one or more of uncontrolled growth ( / .e.. division beyond normal limits), invasion (i.e.. intrusion on and destruction of adjacenttissues), and metastasis (i.e., spread to other locations in the body via lymph or blood). As used herein, the term “metastasize” refers to the spread of cancer from one part of the body to another. A tumor formed by cells drat have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. As used herein, the term “benign” or “non-malignanf ’ refers to tumors that may grow larger but do not spread to other parts of the body. Benign tumors are self-limited and typically do not invade or metastasize.

[0309] A “cancer cell” or “tumor cell” refers to an individual cell of a cancerous growth or tissue. A tumor refers generally to a swelling or lesion fonned by an abnormal growth of cells, which may be benign, pre -malignant, or malignant. Most cancer cells fonn tumors, but some, e.g.. leukemia, do not necessarily form tumors. For those cancer cells that form tumors, the terns cancer (cell) and tumor (cell) are used interchangeably.

[0310] As used herein the term "neoplasm" refers to any new and abnormal growth of tissue, e.g., an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues. Thus, a neoplasm can be a benign neoplasm, premalignant neoplasm, or a malignant neoplasm.

[0311] A subject that has a cancer or a tumor is a subject having objectively measurable cancer cells present in the subject’s body. Included in this definition are malignant, actively proliferative cancers, as well as potentially dormant tumors or micrometastases. Cancers which migrate from their original location and seed other vital organs can eventually lead to the death of the subject through the functional deterioration of the affected organs.

[0312] Examples of cancer include but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, leukemia, basal cell carcinoma, biliary tract cancer; bladder cancer; bone cancer; brain and CNS cancer; breast cancer; cancer of the peritoneum; cervical cancer; choriocarcinoma; colon and rectmn cancer; connective tissue cancer; cancer of the digestive system; endometrial cancer; esophageal cancer; eye cancer; cancer of the head and neck; gastric cancer (including gastrointestinal cancer); glioblastoma (GBM); hepatic carcinoma; hepatoma; intra-epithelial neoplasm.; kidney or renal cancer; larynx cancer; leukemia; liver cancer; lung cancer (e.g. , small -cell lung cancer, nonsmall cell lung cancer, adenocarcinoma of the lung, and squamous carcinoma of the lung); lymphoma including Hodgkin’s and non-Hodgkin‘s lymphoma; melanoma; myeloma; neuroblastoma; oral cavity cancer (e.g., lip, tongue, mouth, and pharynx); ovarian cancer; pancreatic cancer; prostate cancer; retinoblastoma; rhabdomyosarcoma; rectal cancer; cancer of the respiratory system; salivary gland carcinoma; sarcoma; skin cancer; squamous cell cancer; stomach cancer; testicular cancer; thyroid cancer; uterine or endometrial cancer; cancer of the urinary' system; vulval cancer; as well as other carcinomas and sarcomas; as well as B-cell lymphoma (including low grade / follicular non-Hodgkin’s lymphoma (NHL): small lymphocytic (SL) NHL; intermediate grade / follicular NHL; intermediate grade diffuse NHL; high grade immunoblastic NHL; high grade lymphoblastic NHL; high grade smallnon-clcavcd cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related ly mphoma; and Waldenstrom's Macroglobulinemia); chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); Hairy cell leukemia; chronic myeloblastic leukemia; and post-transplant lymphoproliferative disorder (PTLD), as well as abnormal vascular proliferation associated with phakomatoses, edema (such as that associated with brain tumors), and Meigs' syndrome.

[0313] A “cancer cell" is a cancerous, pre-cancerous, or transformed cell, either in vivo, ex vivo, or in tissue culture, that has spontaneous or induced phenotypic changes that do not necessarily involve the uptake of new genetic material. Although transformation can arise from infection with a transforming virus and incorporation of new genomic nucleic acid, or uptake of exogenous nucleic acid, it can also arise spontaneously or following exposure to a carcinogen, thereby mutating an endogenous gene. Transformation / cancer is associated with, e.g., morphological changes, immortalization of cells, aberrant growth control, foci formation, anchorage independence, malignancy, loss of contact inhibition and density limitation of growth, growth factor or serum independence, tumor specific markers, invasiveness or metastasis, and tumor growth in suitable animal hosts such as nude mice.

[0314] In some embodiments of any of the apsects, the composition as described herein, e.g., a composition comprising at least one IL as described herein in combination with at least one active compound, is administered as a monotherapy, e.g.. another treatment for the condition is not administered to the subject.

[0315] In some embodiments of any of the aspects, the methods described herein can further comprise administering a second agent and / or treatment to the subject, e.g. as part of a combinatorial therapy, either in the composition described herein, e.g., a composition comprising at least one IL as described herein in combination with at least one active compound, or as a separate formulation. For example, non-limiting examples of a second agent and / or treatment for treatment of cancer can include radiation therapy , surgery, gemcitabine, cisplastin, paclitaxel, carboplatin, bortezomib, AMG479, vorinostat, rituximab, temozolomide, rapamycin, ABT-737, PI- 103; alkylating agents such as thiotepa and CYTOXAN® cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylenephosphoramide, triethiylenethiophosphoramide and trimethylolomelamine; acetogenins (especially bullatacin and bullatacinone); a camptothecin (including the synthetic analogue topotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB1-TM1); eleutherobin; pancrati statin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine. cholophosphamide, estramustine, ifosfamide. mechlorethamine. mechlorethamine oxide hydrochloride, melphalan. novembichin.phcncstcrinc, prcdnimustinc, trofosfamidc, uracil mustard; nitrosurcas such as carmustinc, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics e.g., calicheamicin, especially calicheamicin gammall and calicheamicin omegall (see, e.g., Agnew, Chem. Inti. Ed. Engl., 33: 183-186 (1994)); dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antiobiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, ADR1AMYC1N® doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2- pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin. quelamycin. rodorubicin, streptonigrin. streptozocin, tubercidin, ubenimex. zinostatin, zorubicin; anti -metabolites such as methotrexate and 5 -fluorouracil (5-FU); folic acid analogues such as denopterin. methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, didcoxyuridine. doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol. mepitiostane, testolactone; anti-adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfonnithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxy urea; lentinan; lonidainine; maytansinoids such as maytansinc and ansamitocins; mitoguazonc; mitoxantronc; mopidanmol; nitracrinc; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, Oreg.); razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2"-trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside ("Ara-C"); cyclophosphamide; thiotepa; taxoids. e.g., TAXOL® paclitaxel (Bristol-Myers Squibb Oncology, Princeton, N.J.), ABRAXANE® Cremophor-free, albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners. Schaumberg, Ill.), and TAXOTERE® doxetaxel (Rhone-Poulenc Rorer. Antony , France); chloranbucil; GEMZAR® gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin, oxaliplatin and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; NAVELBINE. RTM. vinorelbine; novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; irinotecan (Camptosar, CPT-11) (including the treatment regimen of irinotecan with 5-FU and leucovorin); topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such asretinoic acid; capccitabinc; combrctastatin; leucovorin (LV); oxaliplatin, including the oxaliplatin treatment regimen (FOLFOX); lapatinib (Tykerb.RTM.); inhibitors of PKC -alpha, Raf, H-Ras, EGFR (e.g., erlotinib (Tarceva®)) and VEGF-A that reduce cell proliferation and pharmaceutically acceptable salts, acids or derivatives of any of the above. In addition, the methods of treatment can further include the use of radiation or radiation therapy. Further, the methods of treatment can further include the use of surgical treatments.

[0316] In certain embodiments, an effective dose of a composition described herein, e.g., a composition comprising at least one IL as described herein in combination with at least one active compound, can be administered to a patient once. In certain embodiments, an effective dose a composition described herein, e.g.. a composition comprising at least one IL as described herein in combination with at least one active compound, can be administered to a patient repeatedly. For systemic administration, subjects can be administered a therapeutic amount of a composition described herein, e.g., a composition comprising at least one IL as described herein in combination with at least one active compound, such as, e.g. 0. 1 mg / kg, 0.5 mg / kg, 1.0 mg / kg, 2.0 mg / kg. 2.5 mg / kg, 5 mg / kg, 10 mg / kg, 15 mg / kg. 20 mg / kg. 25 mg / kg. 30 mg / kg, 40 mg / kg, 50 mg / kg, or more. In some embodiments of any of the aspects, the at least one active compound is present in the combination at a dose of from about 1.0-40.0 mg / kg. In some embodiments of any of the aspects, the at least one active compound is present in the combination at a dose of from 1.0-40.0 mg / kg. In some embodiments of any of the aspects, the at least one active compound is present in the combination at a dose of from about 1.0-20.0 mg / kg. In some embodiments of any of the aspects, the at least one active compound is present in the combination at a dose of from 1.0-20.0 mg / kg.

[0317] In some embodiments, the active compound is insulin and the concentration or dosage of insulin can be from about lU / kg to about 20 U / kg. In some embodiments, the active compound is insulin and the concentration or dosage of insulin can be from lU / kg to 20 U / kg. hr some embodiments, the active compound is insulin and the concentration or dosage of insulin can be less than 20 U / kg. In some embodiments, the active compound is insulin and the concentration or dosage of insulin can be from about 2U / kg to about 10 U / kg. In some embodiments, the active compound is insulin and the concentration or dosage of insulin can be from 2U / kg to 10 U / kg. In some embodiments, the active compound is insulin and the concentration or dosage of insulin can be from about 2U / kg to about 5 U / kg. In some embodiments, the active compound is insulin and the concentration or dosage of insulin can be from 2U / kg to 5 U / kg. In some embodiments, the active compound is insulin and the concentration or dosage of insulin can be from about 5U / kg to about 10 U / kg. In some embodiments, the active compound is insulin and the concentration or dosage of insulin can be from 5U / kg to 10 U / kg. In some embodiments, the active compound is insulin and the concentration or dosage of insulin can be 2U / kg, 5 U / kg. or 10 U / kg.

[0318] In one aspect of any of the embodiments, described herein is a method of treating a disease in a subject in need thereof by administering to the subject an active compound in combination with tire at least one IL as described herein by into the affected tissue by injection. In some embodiments, the affected tissue is tissue comprising diseased cells. In some embodiments, the affected tissue is tissue displaying symptoms of the disease. Non-limiting examples of suitable affected tissues include tumor tissue, fat tissue, adipose tissue, or the like. In some embodiments of any of the aspects, suitable affected tissues include tumor tissue, fat tissue, adipose tissue, or the like. In some embodiments of any of the aspects, the disease is a disease arising from tissue growth, e.g., unwanted, aberrant, or pathological tissue growth. A disease arising from tissue growth can be any disease caused by or characterized by, a rate of tissue growth, location of tissue growth, or pattem / structure of tissue growth which differs from what is normal for that tissue type in a healthy subject. Non-limiting examples of such diseases are tumors, cancer, fat / obesity, and / or hyperplasia. In some embodiments of any of tire aspects, such diseases are tumors, cancer, fat / obesity. and / or hyperplasia.

[0319] Enzyme inhibitors are a treatment option for a number of conditions, including diabetes, where, for example, insulin-degrading enzyme inhibitors. ACE inhibitors, and alapha-glucosidase inhibitors have all been explored as therapeutic approaches. Safe, effective enzyme inhibitors are therefore of interest in the treatment of a number of conditions. Without wishing to be bound by theory , it is contemplated herein that the ILs described herein can exhibit enzyme inhibition activity. Accordingly, in one aspect of any of the embodiments, described herein is a method of treating diabetes, ulcers, cancer, or fibrosis in a subject in need thereof, the method comprising administering to the subject a composition comprising at least one IL as described herein. In some embodiments, the composition does not comprise a further therapeutically active agent.

[0320] Fibrotic conditions benefit from the production and / or maintenance of the extracellular matrix by reducing the accumulation of scar tissue in favor of extracellular matrix. As used herein, “fibrosis” refers to die formation of fibrous tissue as a reparative or reactive process, rather than as a normal constituent of an organ or tissue. Fibrosis is characterized by fibroblast accumulation and collagen deposition in excess of normal deposition in any particular tissue. Fibrosis can occur as the result of inflammation, irritation, or healing. A subject in need of treatment for a fibrotic condition is any subject having, or diagnosed as having, or at risk of having a fibrotic condition. Non-limiting examples of fibrotic conditions include, but are not limited to pulmonary fibrosis; scarring; scarring of the skin; trauma; a wound; chronic wounds (e g. as in diabetes patients), corneal defects: corneal ulceration; corneal wounds; diabetic ulcer; ulcer; sepsis; arthritis: idiopathic pulmonary fibrosis; cystic fibrosis; cirrhosis; endomyocardial fibrosis: mediastinal fibrosis; myelofibrosis: retroperitoneal fibrosis: progressive massive fibrosis: nephrogenic systemic fibrosis; Crohn’s disease: keloid; scleroderma; systemic sclerosis; arthrofibrosis; adhesive capsulitis; lung fibrosis; liver fibrosis; kidneyfibrosis; heart fibrosis; vascular fibrosis; skin fibrosis; eye fibrosis; bone marrow fibrosis; asthma; sarcoidosis; COPD; emphysema; nschistomasomiasis; cholangitis; diabetic nephropathy: lupus nephritis; postangioplasty aterial restenosis; atherosclerosis; bum scarring; hypertrophic scarring; nephrogenic fibrosing dermatopathy; postcataract surgery; proliferative vitreoretinopathy; Peyronie’s disease; Duputren's contracture; dermatomyositis; and graft versus host disease.

[0321] As used herein, “ulcer” refers to a break or disruption of a bodily membrane. In some embodiments, the ulcer can be caused by inflammation and / or necrosis of the affected tissue. Ulcers can be skin ulcers (e.g., pressure ulcers, diabetic ulcers, ulcerative dermatitis, and the like), a comeal ulcer, an oral ulcer, a peptic ulcer, a venousucler, a stress ulcer, or ulcerative colitis.

[0322] In some embodiments, after an initial treatment regimen, the treatments can be administered on a less frequent basis. For example, after treatment biweekly for three months, treatment can be repeated once per month, for six months or a year or longer. Treatment according to the methods described herein can reduce levels of a marker or symptom of a condition, by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80 % or at least 90% or more.

[0323] The dosage of a composition as described herein can be determined by a physician and adjusted, as necessary, to suit observed effects of the treatment. With respect to duration and frequency of treatment, it is typical for skilled clinicians to monitor subjects in order to determine when the treatment is providing therapeutic benefit, and to determine whether to increase or decrease dosage, increase or decrease administration frequency, discontinue treatment, resume treatment, or make other alterations to the treatment regimen. The dosing schedule can vary from once a week to daily depending on a number of clinical factors, such as the subject's sensitivity to the active compound. The desired dose or amount of activation can be administered at one time or divided into subdoses, e.g., 2-4 subdoses and administered over a period of time, e.g., at appropriate interv als through the day or other appropriate schedule. In some embodiments, administration can be chronic, e.g., one or more doses and / or treatments daily over a period of weeks or months. Examples of dosing and / or treatment schedules are administration daily, twice daily, three times daily or four or more times daily over a period of 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, or 6 months, or more. A composition described herein, e.g., a composition comprising at least one IL in combmation with at least one active compound, can be administered over a period of time, such as over a 5 minute, 10 minute, 15 minute, 20 minute, or 25 minute period.

[0324] The dosage ranges for the administration of the compositions described herein, according to the methods described herein depend upon, for example, the form of the active compound, its potency, and the extent to which symptoms, markers, or indicators of a condition described herein are desired to be reduced, for example the percentage reduction desired for symptoms or markers. The dosage should not be so large as to cause adverse side effects. Generally, the dosage will vary withthe age, condition, and sex of the patient and can be determined by one of skill in the art. The dosage can also be adjusted by the individual physician in tire event of any complication.

[0325] The efficacy of a composition described in, e.g. the treatment of a condition described herein, or to induce a response as described herein can be determined by the skilled clinician.However, a treatment is considered “effective treatment," as the term is used herein, if one or more of the signs or symptoms of a condition described herein are altered in a beneficial manner, other clinically accepted symptoms are improved, or even ameliorated, or a desired response is induced e.g., by at least 10% following treatment according to the methods described herein. Efficacy can be assessed, for example, by measuring a marker, indicator, symptom, and / or the incidence of a condition treated according to the methods described herein or any other measurable parameter appropriate. Efficacy can also be measured by a failure of an individual to worsen as assessed by hospitalization, or need for medical interventions (i.e.. progression of the disease is halted). Methods of measuring these indicators are known to those of skill in the art and / or are described herein. Treatment includes any treatment of a disease in an individual or an animal (some non-limiting examples include a human or an animal) and includes: (1) inhibiting the disease, e.g.. preventing a worsening of symptoms (e.g. pain or inflammation); or (2) relieving the severity of the disease, e.g.. causing regression of symptoms. An effective amount for the treatment of a disease means that amount which, when administered to a subject in need thereof, is sufficient to result in effective treatment as that term is defined herein, for that disease. Efficacy of an agent can be determined by assessing physical indicators of a condition or desired response. It is well within the ability of one skilled in the art to monitor efficacy of administration and / or treatment by measuring any one of such parameters, or any combination of parameters. Efficacy can be assessed in animal models of a condition described herein, for example treatment of diabetes or cancer. When using an experimental animal model, efficacy of treatment is evidenced when a statistically significant change in a marker is observed.

[0326] In vitro and animal model assays are provided herein which allow the assessment of a given dose of a composition described herein, e.g., a composition comprising at least one IL in combination with at least one active compound.

[0327] In some embodiments of any of the aspects, the subject administered a composition comprising at least one IL as described herein, e.g., in combination with an active compound is a subject having, diagnosed as having, or in need of treatment for obesity, excess weight, or prevention of weight gain. In some embodiments, the subject is overweight. The methods described herein comprises methods of treating obesity, reducing weight gain, preventing weight gain, promoting weight loss, and the like. Such methods can, e.g., promote metabolic health, be pursued for aesthetic reasons, and / or prepare patients for surgical interventions which are counter indicated for those with high BMIs or weights. In some embodiments, weight loss can be medically necessary and / ormedically indicated, c.g. when the subject is overw eight and / or obese. In some embodiments, weight loss can be for cosmetic purposes, e.g. when the subject desires to lose weight whether or not weight loss is medically necessary and / or medically indicated.

[0328] The term "obesity" refers to excess fat in the body. Obesity can be determined by any measure accepted and utilized by those of skill in the art. Currently, an accepted measure of obesity is body mass index (BMI), which is a measure of body weight in kilograms relative to the square of height in meters. Generally, for an adult over age 20, a BMI between about 18.5 and 24.9 is considered normal, a BMI between about 25.0 and 29.9 is considered overweight, a BMI at or above about 30.0 is considered obese, and a BMI at or above about 40 is considered morbidly obese. (See, e.g., Gallagher et al. (2000) Am J Clin Nutr 72:694-701.) These BMI ranges are based on the effect of body weight on increased risk for disease. Some common conditions related to high BMI and obesity include cardiovascular disease, high blood pressure (i.e.. hypertension), osteoarthritis, cancer, and diabetes. Although BMI correlates with body fat, the relation between BMI and actual body fat differs with age and gender. For example, women are more likely to have a higher percent of body fat than men for the same BMI. Furthermore, the BMI threshold that separates normal, overweight, and obese can vary, e.g. with age. gender, ethnicity, fitness, and body type, amongst other factors. In some embodiments, a subject with obesity can be a subject with a body mass index of at least about 25 kg / m2prior to administration of a treatment as described herein. In some embodiments, a subject with obesity can be a subject with a body mass index of at least about 30 kg / m2prior to administration of a treatment as described herein.

[0329] In some embodiments of any of the aspects, the subject administered a composition comprising at least one IL as described herein, e.g., in combination with at least one active compound is a subject having, diagnosed as having, or in need of treatment for a metabolic disorder or metabolic syndrome. The term “metabolic disorder” refers to any disorder associated with or aggravated by impaired or altered glucose regulation or glycemic control, such as, for example, insulin resistance. Such disorders include, but are not limited to obesity; excess adipose tissue; diabetes; fatty liver disease; non-alcoholic fatty liver disease; metabolic syndrome; dyslipidemia; hypertension; hyperglycemia; and cardiovascular disease. “Metabolic syndrome”, which is distinct from metabolic disorder, refers to a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. A number of definitions of metabolic syndrome have been established, e.g.. by the American Heart Association and the International Diabetes Foundation. As but one example, the WHO defines metabolic syndrome as the presence of any one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance and two of the following: blood pressure equal to or greater than 140 / 90 mmHg, dyslipidemia, central obesity, and microalbuminuria. In some embodiments, the metabolic disorder can be selected from the group consisting of: obesity; excess adipose tissue; diabetes; and cardiovascular disease.

[0330] The uptake of many active compounds, c.g., pharmaceutically active compounds, can be improved by delivering the compounds in solvents. However, such approaches are often unsuitable for in vivo use because most such solvents demonstrate toxic side effects and / or act as irritants to the point of delivery. Described herein are methods and compositions which can provide low toxicity with improved deliver) kinetics.

[0331] In some embodiments of any of the aspects, a composition described herein does not comprise a polysorbate surfactant, a polysorbate, an animo acid monomer, a disaccharide, a salt other that an ionic liquid, a copolymer, or a hyaluronidase. In some embodiments of any of the aspects, a composition described herein does not comprise a polysorbate surfactant. In some embodiments of any of the aspects, a composition described herein does not comprise a polysorbate. In some embodiments of any of the aspects, a composition described herein does not comprise an animo acid monomer. In some embodiments of any of the aspects, a composition described herein does not comprise a disaccharide. In some embodiments of any of the aspects, a composition described herein does not comprise a salt other that an ionic liquid. In some embodiments of any of the aspects, a composition described herein does not comprise a copolymer. In some embodiments of any of the aspects, a composition described herein does not comprise a hyaluronidase.

[0332] For convenience, the meaning of some terms and phrases used in the specification, examples, and appended claims, are provided below. Unless stated otherwise, or implicit from context, the following terms and phrases include the meanings provided below. The definitions are provided to aid in describing particular embodiments, and are not intended to limit the claimed invention, because the scope of the invention is limited only by the claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. If there is an apparent discrepancy between the usage of a term in the art and its definition provided herein, the definition provided within the specification shall prevail.

[0333] For convenience, certain terms employed herein, in the specification, examples and appended claims are collected here.

[0334] CAGE (Choline And GEranate) is an ionic liquid comprising the cation choline (see, c.g., Formula II) and the anion geranate or geranic acid (see, c.g., Formulas III and IV). Preparation of CAGE can be, e g., as described in International Patent Publication WO 2015 / 066647; which is incorporated by reference herein in its entirety, or as described in the examples herein.Formula IIFormula IV

[0335] The terms “decrease", “reduced”, “reduction”, or “inhibit” are all used herein to mean a decrease by a statistically significant amount. In some embodiments, “reduce,” “reduction" or “decrease" or “inhibit” typically means a decrease by at least 10% as compared to a reference level (e.g. the absence of a given treatment or agent) and can include, for example, a decrease by at least about 10%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%. at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%. at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%. at least about 98%, at least about 99% . or more. As used herein,“reduction” or “inhibition” does not encompass a complete inhibition or reduction as compared to a reference level. “Complete inhibition” is a 100% inhibition as compared to a reference level. A decrease can be preferably down to a level accepted as within the range of normal for an individual without a given disorder.

[0336] The terms “increased”, “increase”, “enhance”, or “activate” are all used herein to mean an increase by a statically significant amount. In some embodiments, the terms “increased”, “increase”, “enhance”, or “activate” can mean an increase of at least 10% as compared to a reference level, forexample an increase of at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90% or up to and including a 100% increase or any increase between 10-100% as compared to a reference level, or at least about a 2-fold, or at least about a 3 -fold, or at least about a 4-fold, or at least about a 5-fold or at least about a 10-fold increase, or any increase between 2-fold and 10-fold or greater as compared to a reference level. In the context of a marker or symptom, a “increase” is a statistically significant increase in such level.

[0337] As used herein, a "subject" means a human or animal. Usually the animal is a vertebrate such as a primate, rodent, domestic animal or game animal. Primates include chimpanzees, cynomologus monkeys, spider monkeys, and macaques, e.g.. Rhesus. Rodents include mice, rats, woodchucks, ferrets, rabbits and hamsters. Domestic and game animals include cows, horses, pigs, deer, bison, buffalo, feline species, e.g.. domestic cat, canine species, e.g., dog, fox, wolf, avian species, e.g., chicken, emu. ostrich, and fish, e.g., trout, catfish and salmon. In some embodiments, the subject is a mammal, e.g., a primate, e.g., a human. The terms, “individual,” “patient” and “subject” are used interchangeably herein.

[0338] Preferably, the subject is a mammal. The mammal can be a human, non-human primate, mouse, rat. dog, cat, horse, or cow, but is not limited to these examples. Mammals other than humans can be advantageously used as subjects that represent animal models of conditions described herein. A subject can be male or female.

[0339] A subject can be one who has been previously diagnosed with or identified as suffering from or having a condition in need of treatment or one or more complications related to such a condition, and optionally, have already undergone treatment for the condition or the one or more complications related to the condition. Alternatively, a subject can also be one who has not been previously diagnosed as having the condition or one or more complications related to the condition. For example, a subject can be one who exhibits one or more risk factors for the condition or one or more complications related to the condition or a subject who does not exhibit risk factors.

[0340] A “subject in need” of treatment for a particular condition can be a subject having that condition, diagnosed as having that condition, or at risk of developing that condition.

[0341] As used herein, the terms “protein" and “polypeptide" are used interchangeably herein to designate a series of amino acid residues, connected to each other by peptide bonds between the alpha-amino and carboxy groups of adjacent residues. The terms "protein", and "polypeptide" refer to a polymer of amino acids, including modified amino acids (e.g., phosphorylated, glycated, glycosylated, etc.) and amino acid analogs, regardless of its size or function. "Protein" and “polypeptide” are often used in reference to relatively large polypeptides, whereas the term "peptide" is often used in reference to small polypeptides, but usage of these terms in the art overlaps. The terms "protein" and "polypeptide" are used interchangeably herein when referring to a gene product andfragments thereof. Thus, exemplary polypeptides or proteins include gene products, naturally occurring proteins, homologs, orthologs, paralogs, fragments and other equivalents, variants, fragments, and analogs of the foregoing.

[0342] In the various embodiments described herein, it is further contemplated that variants (naturally occurring or otherwise), alleles, homologs, conservatively modified variants, and / or conservative substitution variants of any of the particular polypeptides described are encompassed. As to amino acid sequences, one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters a single amino acid or a small percentage of amino acids in the encoded sequence is a "conservatively modified variant" where the alteration results in the substitution of an amino acid with a chemically similar amino acid and retains the desired activity of the polypeptide. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles consistent with the disclosure.

[0343] A given amino acid can be replaced by a residue having similar physiochemical characteristics, e.g.. substituting one aliphatic residue for another (such as lie, Vai. Leu, or Ala for one another), or substitution of one polar residue for another (such as between Lys and Arg; Glu and Asp; or Gin and Asn). Other such conservative substitutions, e g., substitutions of entire regions having similar hydrophobicity7characteristics, are well known. Polypeptides comprising conservative amino acid substitutions can be tested in any one of the assays described herein to confirm that a desired activity, e.g. the activity and specificity7of a native or reference polypeptide is retained.

[0344] Amino acids can be grouped according to similarities in the properties of their side chains (in A. L. Lehninger, in Biochemistry, second ed., pp. 73-75, Worth Publishers, New York (1975)): (1) non-polar: Ala (A), Vai (V), Leu (L), He (I). Pro (P), Phe (F). Trp (W), Met (M); (2) uncharged polar: Gly (G), Ser (S), Thr (T), Cys (C), Tyr (Y), Asn (N). Gin (Q); (3) acidic: Asp (D), Glu (E); (4) basic: Lys (K), Arg (R), His (H). Alternatively, naturally occurring residues can be divided into groups based on common side-chain properties: (1) hydrophobic: Norleucine, Met, Ala, Vai, Leu, He; (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gin; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that influence chain orientation: Gly, Pro; (6) aromatic: Trp, Tyr, Phe. Non-conservative substitutions will entail exchanging a member of one of these classes for another class. Particular conservative substitutions include, for example; Ala into Gly or into Ser; Arg into Lys; Asn into Gin or into His; Asp into Glu; Cys into Ser; Gin into Asn; Glu into Asp; Gly into Ala or into Pro; His into Asn or into Gin; He into Leu or into Vai; Leu into He or into Vai; Lys into Arg, into Gin or into Glu; Met into Leu, into Tyr or into lie: Phe into Met, into Leu or into Tyr; Ser into Thr: Thr into Ser; Trp into Tyr; Tyr into Trp; and / or Phe into Vai, into He or into Leu.

[0345] In some embodiments, the polypeptide described herein (or a nucleic acid encoding such a polypeptide) can be a functional fragment of one of the amino acid sequences described herein. Asused herein, a “functional fragment” is a fragment or segment of a peptide which retains at least 50% of the wildly pc reference polypeptide’s activity according to the assays described below herein. A functional fragment can comprise conservative substitutions of the sequences disclosed herein.

[0346] In some embodiments, the polypeptide described herein can be a variant of a sequence described herein. In some embodiments, the variant is a conservatively modified variant. Conservative substitution variants can be obtained by mutations of native nucleotide sequences, for example. A “variant," as referred to herein, is a polypeptide substantially homologous to a native or reference polypeptide, but which has an amino acid sequence different from that of the native or reference polypeptide because of one or a plurality of deletions, insertions or substitutions. Variant polypeptide- encoding DNA sequences encompass sequences that comprise one or more additions, deletions, or substitutions of nucleotides when compared to a native or reference DNA sequence, but that encode a variant protein or fragment thereof that retains activity. A wide variety of PCR-based site-specific mutagenesis approaches are known in the art and can be applied by the ordinarily skilled artisan.

[0347] A variant amino acid or DNA sequence can be at least 90%, at least 91%, at least 92%, at least 93%, at least 94%. at least 95%, at least 96%. at least 97%. at least 98%, at least 99%, or more, identical to a native or reference sequence. The degree of homology (percent identity) between a native and a mutant sequence can be determined, for example, by comparing the two sequences using freely available computer programs commonly employed for this purpose on the world wide web (e g. BLASTp or BLASTn with default settings).

[0348] In some embodiments of any of the aspects, a variant can be a polypeptide having at least 90%, at least 95%, at least 98% or greater sequence homology to one of the reference sequences provided herein and retaining the wild-type activity of that reference sequence, e.g., incretin activity. In some embodiments of any of the aspects, a variant can be a polypeptide having at least 90%, at least 95%, at least 98% or greater sequence homology’ to one of the naturally -occurring reference sequences provided herein and retaining the wild-type activity’ of that reference sequence, e.g., incretin activity. In some embodiments of any of the aspects, a variant can be a naturally -occurring polypeptide having at least 90%, at least 95%, at least 98% or greater sequence homology to one of the reference sequences provided herein and retaining the wild-type activity of that reference sequence, e.g., incretin activity.

[0349] Alterations of the native amino acid sequence can be accomplished by any of a number of techniques known to one of skill in the art. Mutations can be introduced, for example, at particular loci by synthesizing oligonucleotides containing a mutant sequence, flanked by restriction sites enabling ligation to fragments of the native sequence. Following ligation, the resulting reconstructed sequence encodes an analog having the desired amino acid insertion, substitution, or deletion. Alternatively, oligonucleotide-directed site-specific mutagenesis procedures can be employed to provide an altered nucleotide sequence having particular codons altered according to the substitution.deletion, or insertion required. Techniques for making such alterations arc very well established and include, for example, those disclosed by Walder et al. (Gene 42: 133, 1986); Bauer et al. (Gene 37:73, 1985); Craik (BioTechniques, January 1985, 12-19); Smith et al. (Genetic Engineering: Principles and Methods, Plenum Press, 1981); and U.S. Pat. Nos. 4,518,584 and 4,737,462, which are herein incorporated by reference in their entireties. Any cysteine residue not involved in maintaining the proper conformation of the polypeptide also can be substituted, generally with serine, to improve the oxidative stability of the molecule and prevent aberrant crosslinking. Conversely, cysteine bond(s) can be added to the polypeptide to improve its stability or facilitate oligomerization.

[0350] As used herein, the term “antibody” refers to immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e., molecules that contain an antigen binding site that immunospecifically binds an antigen. The term also refers to antibodies comprised of two immunoglobulin heavy chains and two immunoglobulin light chains as well as a variety of fonns including full length antibodies and antigen-binding portions thereof; including, for example, an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a Fab. a Fab', a F(ab')2. a Fv. a disulfide linked Fv. a scFv. a single domain antibody (dAb), a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, a bispecific antibody, a functionally active epitope-binding portion thereof, and / or bifunctional hybrid antibodies. Each heavy chain is composed of a variable region of said heavy chain (abbreviated here as HCVR or VH) and a constant region of said heavy chain. The heavy chain constant region consists of three domains CHI, CH2 and CH3. Each light chain is composed of a variable region of said light chain (abbreviated here as LCVR or VL) and a constant region of said light chain. The light chain constant region consists of a CL domain. The VH and VL regions may be further divided into hypervariable regions referred to as complementarity -determining regions (CDRs) and interspersed with conserved regions referred to as framework regions (FR). Each VH and VL region thus consists of three CDRs and four FRs which are arranged from the N terminus to the C terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. This structure is well known to those skilled in the art.

[0351] As used herein, the term “antibody reagent" refers to a polypeptide that includes at least one immunoglobulin variable domain or immunoglobulin variable domain sequence and which specifically binds a given antigen. An antibody reagent can comprise an antibody or a polypeptide comprising an antigen-binding domain of an antibody. In some embodiments, an antibody reagent can comprise a monoclonal antibody or a polypeptide comprising an antigen-binding domain of a monoclonal antibody. For example, an antibody can include a heavy (H) chain variable region (abbreviated herein as VH), and a light (L) chain variable region (abbreviated herein as VL). In another example, an antibody includes two heavy (H) chain variable regions and two light (L) chain variable regions. The term "antibody reagent" encompasses antigen-binding fragments of antibodies(c.g., single chain antibodies, Fab and sFab fragments, F(ab')2, Fd fragments, Fv fragments, seFv, and domain antibodies (dAb) fragments as well as complete antibodies.

[0352] Antibodies and / or antibody reagents can include an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a fully human antibody, a Fab, a Fab', a F(ab')2, a Fv, a disulfide linked Fv, a seFv, a single domain antibody, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, a bispecific antibody, and a functionally active epitope-binding portion thereof.

[0353] As used herein, the term “nanobody” or single domain antibody (sdAb) refers to an antibody comprising the small single variable domain (VHH) of antibodies obtained from camelids and dromedaries. Antibody proteins obtained from members of the camel and dromedary (Camelus baclrianus and Calelus dromaderius) family including new world members such as llama species (Lama paccos, Lama glama and Lama vicugna) have been characterized with respect to size, structural complexity and antigenicity for human subjects. Certain IgG antibodies from this family of mammals as found in nature lack light chains, and are thus structurally distinct from the typical four chain quaternary structure having two heavy and two light chains, for antibodies from other animals. See PCT / EP93 / 02214 (WO 94 / 04678 published 3 Mar. 1994; which is incorporated by reference herein in its entirety).

[0354] A region of the camelid antibody which is the small single variable domain identified as VHH can be obtained by genetic engineering to yield a small protein having high affinity for a target, resulting in a low molecular weight antibody-derived protein known as a “camelid nanobody”. See U.S. Pat. No. 5,759,808 issued Jun. 2, 1998; see also Stijlemans, B. et al., 2004 J Biol Chem 279: 1256-1261; Dumoulin, M. et al., 2003 Nature 424: 783-788; Pleschberger, M. et al. 2003 Bioconjugate Chem 14: 440-448; Cortez-Retamozo, V. et al. 2002 Int J Cancer 89: 456-62; and Lauwereys, M. et al. 1998 EMBO J. 17: 3512-3520; each of which is incorporated by reference herein in its entirety. Engineered libraries of camelid antibodies and antibody fragments are commercially available, for example, from Ablynx, Ghent, Belgium. As with other antibodies of non-huinan origin, an amino acid sequence of a camelid antibody can be altered recombinantly to obtain a sequence that more closely resembles a human sequence, i.e., the nanobody can be “humanized”. Thus the natural low antigenicity of camelid antibodies to humans can be further reduced.

[0355] The camelid nanobody has a molecular weight approximately one-tenth that of a human IgG molecule and the protein has a physical diameter of only a few nanometers. One consequence of the small size is the ability of camelid nanobodies to bind to antigenic sites that are functionally invisible to larger antibody proteins, i.e., camelid nanobodies are useful as reagents detect antigens that are otherwise cryptic using classical immunological techniques, and as possible therapeutic agents. Thus yet another consequence of small size is that a camelid nanobody can inhibit as a result of binding to a specific site in a groove or narrow cleft of a target protein, and hence can serve in acapacity that more closely resembles the function of a classical low molecular weight drug than that of a classical antibody. The low molecular weight and compact size further result in camelid nanobodies being extremely thermostable, stable to extreme pH and to proteolytic digestion, and poorly antigenic. See U.S. patent application 20040161738 published Aug. 19, 2004; which is incorporated by reference herein in its entirety. These features combmed with the low antigenicity to humans indicate great therapeutic potential.

[0356] In some embodiments of any of the aspects, the active compound comprises an antibody or antibody reagent and the anion is a hydrophobic anion comprising carboxylic acid having a pKa of at least 4.0 and a LogP of at least 1.0. In some embodiments of any of the aspects, the active compound comprises an antibody or antibody reagent and the anion is hexenoic acid.

[0357] In some embodiments of any of the aspects, the active compound comprises a nucleic acid and the anion is a hydrophobic anion comprising carboxylic acid having a pKa of at least 4.0 and a LogP of at least 1.0. In some embodiments of any of the aspects, the active compound comprises a nucleic acid and the anion is hexenoic acid.

[0358] In some embodiments of any of the aspects, the active compound comprises an inhibitory nucleic acid. siRNA, pDNA, or mRNA and the anion is a hydrophobic anion comprising carboxy lic acid having a pKa of at least 4.0 and a LogP of at least 1.0. In some embodiments of any of the aspects, the active compound comprises an inhibitory nucleic acid, siRNA, pDNA, or mRNA and the anion is hexenoic acid.

[0359] As used herein, the term “nucleic acid” or “nucleic acid sequence” refers to any molecule, preferably a polymeric molecule, incorporating units of ribonucleic acid, deoxyribonucleic acid or an analog thereof. The nucleic acid can be either single-stranded or double-stranded. A single-stranded nucleic acid can be one nucleic acid strand of a denatured double- stranded DNA. Alternatively, it can be a single-stranded nucleic acid not derived from any double-stranded DNA. In one aspect, the nucleic acid can be DNA. In another aspect, the nucleic acid can be RNA. Suitable DNA can include, e.g., cDNA. Suitable RNA can include, e.g., mRNA.

[0360] As used herein, “inhibitory nucleic acid” refers to a nucleic acid molecule which can inhibit the expression of a target, e.g., double-stranded RNAs (dsRNAs), inhibitory RNAs (iRNAs), and the like. In some embodiments of any of the aspects, the inhibitory nucleic acid can be a silencing RNA (siRNA), microRNA (miRNA), or short hairpin RNA (shRNA). Inhibitory nucleic acids can also include guide sequence molecules (e.g., a guide RNA) that function, e.g., in combination with an enzyme, to induce insertions, deletions, indels, and / or mutations of a target, thereby inhibiting the expression of the target.

[0361] Double-stranded RNA molecules (dsRNA) have been shown to block gene expression in a highly conserved regulatory mechanism known as RNA interference (RNAi). The inhibitory nucleic acids described herein can include an RNA strand (the antisense strand) having a region whichis 30 nucleotides or less in length, i.c., 15-30 nucleotides in length, generally 19-24 nucleotides in length, which region is substantially complementary to at least part the targeted mRNA transcript. The use of these iRNAs enables the targeted degradation of mRNA transcripts, resulting in decreased expression and / or activity of the target.

[0362] As used herein, the term "iRNA'' refers to an agent that contains RNA (or modified nucleic acids as described below herein) and which mediates the targeted cleavage of an RNA transcript via an RNA-induced silencing complex (RISC) pathway. In some embodiments of any of the aspects, an iRNA as described herein effects inhibition of the expression and / or activity of a target. In some embodiments of any of the aspects, contacting a cell with the inhibitor (e.g. an iRNA) results in a decrease in the target mRNA level in a cell by at least about 5%, about 10%, about 20%, about 30%, about 40%, about 50%. about 60%, about 70%, about 80%. about 90%, about 95%, about 99%, up to and including 100% of the target mRNA level found in the cell without the presence of the iRNA. In some embodiments of any of the aspects, administering an inhibitor (e.g. an iRNA) to a subject results in a decrease in the target mRNA level in the subject by at least about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 99%. up to and including 100% of the target mRNA level found in the subject without the presence of the iRNA.

[0363] In some embodiments of any of the aspects, the iRNA can be a dsRNA. A dsRNA includes two RNA strands that are sufficiently complementary to hybridize to form a duplex structure under conditions in which the dsRNA will be used. One strand of a dsRNA (the antisense strand) includes a region of complementarity that is substantially complementary, and generally fully complementary, to a target sequence. The target sequence can be derived from the sequence of an mRNA formed during the expression of the target, e.g., it can span one or more intron boundaries. The other strand (the sense strand) includes a region that is complementary to the antisense strand, such that the two strands hybridize and form a duplex structure when combined under suitable conditions. Generally, the duplex structure is between 15 and 30 base pairs in length inclusive, more generally betw een 18 and 25 base pairs in length inclusive, yet more generally between 19 and 24 base pairs in length inclusive, and most generally between 19 and 21 base pairs in length, inclusive. Similarly, the region of complementarity to the target sequence is between 15 and 30 base pairs in length inclusive, more generally between 18 and 25 base pairs in length inclusive, yet more generally between 19 and 24 base pairs in length inclusive, and most generally between 19 and 21 base pairs in length nucleotides in length, inclusive. In some embodiments of any of the aspects, the dsRNA is between 15 and 20 nucleotides in length, inclusive, and in other embodiments, the dsRNA is between 25 and 30 nucleotides in length, inclusive. As the ordinarily skilled person will recognize, the targeted region of an RNA targeted for cleavage will most often be part of a larger RNA molecule, often an mRNA molecule. Where relevant, a “part” of an mRNA target is a contiguous sequence ofan mRNA target of sufficient length to be a substrate for RNAi-dircctcd cleavage (i.c., cleavage through a RISC pathway). dsRNAs having duplexes as short as 9 base pairs can, under some circumstances, mediate RNAi-directed RNA cleavage. Most often a target will be at least 15 nucleotides in length, preferably 15-30 nucleotides in length.

[0364] Exemplary embodiments of types of inhibitory nucleic acids can include, e.g., siRNA, shRNA. miRNA, and / or amiRNA, which are well known in the art. One skilled in the art would be able to design further siRNA, shRNA, or miRNA to target the nucleic acid sequence of a target gene or gene product (e.g., mRNA), e.g.. using publically available design tools. siRNA, shRNA, or miRNA is commonly made using companies such as Dhannacon (Layfayette. CO) or Sigma Aldrich (St. Louis, MO).

[0365] In some embodiments of any of the aspects, the RNA of an iRNA, e.g., a dsRNA, is chemically modified to enhance stability or other beneficial characteristics. The nucleic acids described herein may be synthesized and / or modified by methods well established in the art. such as those described in “Current protocols in nucleic acid chemistry,” Beaucage, S.L. et al. (Edrs.), John Wiley & Sons. Inc., New York, NY, USA. which is hereby incorporated herein by reference. Modifications include, for example, (a) end modifications, e.g.. 5’ end modifications (phosphorylation, conjugation, inverted linkages, etc.) 3’ end modifications (conjugation. DNA nucleotides, inverted linkages, etc ), (b) base modifications, e.g., replacement with stabilizing bases, destabilizing bases, or bases that base pair with an expanded repertoire of partners, removal of bases (abasic nucleotides), or conjugated bases, (c) sugar modifications (e.g., at the 2’ position or 4’ position) or replacement of the sugar, as well as (d) backbone modifications, including modification or replacement of the phosphodiester linkages. Specific examples of RNA compounds useful in the embodiments described herein include, but are not limited to RNAs containing modified backbones or no natural intemucleoside linkages. RNAs having modified backbones include, among others, those that do not have a phosphorus atom in the backbone. For the purposes of this specification, and as sometimes referenced in the art, modified RNAs that do not have a phosphorus atom in their intemucleoside backbone can also be considered to be oligonucleosides. In some embodiments of any of the aspects, the modified RNA will have a phosphorus atom in its intemucleoside backbone.

[0366] Modified RNA backbones can include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates including 3'-alkylene phosphonates and chiral phosphonates. phosphinates, phosphoramidates including 3'-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those) having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'. Various salts, mixed salts and free acid forms are also included. Modified RNA backbones that do notinclude a phosphorus atom therein have backbones that arc formed by short chain alkyl or cy cloalkyl intemucleoside linkages, mixed heteroatoms and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones: methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; others having mixed N. O, S and CH2 component parts, and oligonucleosides with heteroatom backbones, and in particular -CH2-NH-CH2-. -CH2-N(CH3)-O--CH2--[known as a methylene (methylimino) or MMI backbone], -CH2-O-N(CH3)-CH2-, -CH2-N(CH3)-N(CH3)- -CH2- and --N(CH3)-CH2-CH2-[wherein the native phosphodiester backbone is represented as - O-P-O— CH2— ].

[0367] In other RNA mimetics suitable or contemplated for use in iRNAs, both the sugar and the intemucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for hybridization with an appropriate nucleic acid target compound. One such oligomeric compound, an RNA mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA compounds, the sugar backbone of an RNA is replaced with an amide containing backbone, in particular an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone.

[0368] The RNA of an iRNA can also be modified to include one or more locked nucleic acids (LNA). A locked nucleic acid is a nucleotide having a modified ribose moiety in which the ribose moiety comprises an extra bridge connecting the 2' and 4' carbons. This structure effectively "locks" the ribose in the 3'-endo structural conformation. The addition of locked nucleic acids to siRNAs has been shown to increase siRNA stability in serum, and to reduce off -target effects (Elmen, J. et al., (2005) Nucleic Acids Research 33(l):439-447; Mook, OR. et al., (2007) Mol Cane Ther 6(3):833- 843; Grunweller, A. et al., (2003) Nucleic Acids Research 31(12):3185-3193).

[0369] Modified RNAs can also contain one or more substituted sugar moieties. The iRNAs, e.g., dsRNAs, described herein can include one of the following at the 2' position: OH; F; O-, S-, or N-alkyl; O-, S-, or N-alkeny 1; O-. S- or N-alkynyl; or O-alkyl-O-alkyl, wherein the alk l, alkenyl and alkynyl may be substituted or unsubstituted Cl to CIO alkyl or C2 to CIO alkenyl and alkynyl. Exemplary suitable modifications include O[(CH2)nO] mCH3. O(CH2).nOCH3, O(CH2)nNH2, O(CH2) nCH3, O(CH2)nONH2, and O(CH2)nON[(CH2)nCH3)]2. where n and m are from 1 to about 10. In some embodiments of any of the aspects. dsRNAs include one of the following at the 2' position: Cl to CIO lower alkyl, substituted lower alkyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH. SCH3, OCN, Cl, Br. CN, CF3, OCF3, SOCH3, SO2CH3, ONO2, NO2, N3, NH2. heterocycloalkyl,hctcrocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an iRNA, or a group for improving the pharmacodynamic properties of an iRNA, and other substituents having similar properties. In some embodiments of any of the aspects, the modification includes a 2' methoxyethoxy (2'-O— CH2CH2OCH3, also known as 2'-O-(2-methoxy ethyl) or 2'-M0E) (Martin et al., Helv. Chim. Acta, 1995, 78:486-504) i.e., an alkoxy-alkoxy group. Another exemplary modification is 2'-dimethylaminooxyethoxy, i.e., a O(CH2)2ON(CH3)2 group, also known as 2'- DMAOE, as described in examples herein below, and 2'-dimethylaminoethoxyethoxy (also known in the art as 2'-O-dimethylaminoethoxyethyl or 2'-DMAEOE), i.e., 2'-O— CH2— O— CH2— N(CH2)2. also described in examples herein below.

[0370] Other modifications include 2'-methoxy (2'-OCH3), 2'-aminopropoxy (2'- OCH2CH2CH2NH2) and 2'-fluoro (2'-F). Similar modifications can also be made at other positions on the RNA of an iRNA. particularly the 3' position of the sugar on the 3' terminal nucleotide or in 2'- 5' linked dsRNAs and the 5' position of 5' terminal nucleotide. iRNAs may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar.

[0371] An inhibitory nucleic acid can also include nucleobase (often referred to in the art simply as “base”) modifications or substitutions. As used herein, “unmodified” or “natural” nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases include other synthetic and natural nucleobases such as 5- methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6- methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine. 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine. 5- propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl anal other 8-substituted adenines and guanines, 5- halo, particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7- methylguanine and 7-methyladenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7- daazaadenine and 3 -deazaguanine and 3 -de azaadenine. Certain of these nucleobases are particularly useful for increasing the binding affinity of the inhibitory nucleic acids featured in the invention. These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5 -methylc tosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2°C (Sanghvi, Y. S., Crooke, S. T. and Lebleu, B.. Eds., dsRNA Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are exemplary base substitutions, even more particularly when combined with 2'-O- methoxyethyl sugar modifications.

[0372] The preparation of the modified nucleic acids, backbones, and nucleobases described above are well known in the art.

[0373] Another modification of an inhibitory nucleic acid featured in the invention involves chemically linking to the inhibitory nucleic acid to one or more ligands, moieties or conjugates that enhance the activity, cellular distribution, pharmacokinetic properties, or cellular uptake of the iRNA. Such moieties include but are not limited to lipid moieties such as a cholesterol moiety' (Letsinger et al., Proc. Natl. Acid. Sci. USA, 1989, 86: 6553-6556), cholic acid (Manoharan et al., Biorg. Med. Chem. Let., 1994, 4: 1053-1060), a thioether, e.g., beryl-S-tritylthiol (Manoharan et al., Ann. N.Y. Acad. Sci., 1992, 660:306-309: Manoharan et al., Biorg. Med. Chem. Let., 1993, 3:2765-2770), a thiocholesterol (Oberhauser et al., Nucl. Acids Res., 1992, 20:533-538), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al.. EMBO J, 1991, 10: 1111-1118; Kabanov et al., FEBS Lett., 1990, 259:327-330; Svinarchuk et al., Biochimie, 1993, 75:49-54), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethyl-ammonium l,2-di-O-hexadecyl-rac-glycero-3-phosphonate (Manoharan et al.. Tetrahedron Lett., 1995, 36:3651-3654; Shea et al., Nucl. Acids Res.. 1990. 18:3777-3783), a polyamine or a polyethylene glycol chain (Manoharan et al., Nucleosides & Nucleotides, 1995, 14:969-973), or adamantane acetic acid (Manoharan et al.. Tetrahedron Lett., 1995, 36:3651-3654), a pahnityl moiety’ (Mishra et al., Biochim. Biophys. Acta, 1995, 1264:229-237), or an octadecylamine or hexylamino-carbonyloxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Then, 1996, 277:923-937).

[0374] In some embodiments of the various aspects described herein, the inhibitory nucleic acid is a guide nucleic acid (gNA). As used herein, the terms “guide nucleic acid,” “guide sequence.” “crRNA,” “guide RNA,” “single guide RNA,” “gRNA” or “CRISPR guide sequence” refer to a nucleic acid comprising a sequence that determines tire specificity of an enzyme, e.g., the Cas DNA binding protein of a CRISPR / Cas system, to a polynucleotide target. The gNA can comprise a polynucleotide sequence with at least partial complementarity with a target nucleic acid sequence, sufficient to hybridize with the target nucleic acid sequence and to direct sequence-specific binding of an enzyme, e.g, a nuclease, to the target nucleic acid sequence.

[0375] In some embodiments, the enzyme directed by the gNA is a gene-editing protein, e.g., any nuclease that induces a nick or double-strand break into a desired recognition site. Such enzymes can be native or engineered. These breaks can then be repaired by the cell in one of two ways: non- homologous end joining and homology -directed repair (homologous recombination). In non- homologous end joining (NHEJ). the double-strand breaks are repaired by direct ligation of the break ends to one another. As such, no new nucleic acid material is inserted into the site, although some nucleic acid material may be lost, resulting in a deletion. In homology-directed repair, a donor polynucleotide with homology to the cleaved target DNA sequence can be used as a template for repair of the cleaved target DNA sequence, resulting in the transfer of genetic information from the donor polynucleotide to the target DNA. Therefore, new nucleic acid material may be inserted / copied into the site. The modifications of the target DNA due to NHEJ and / or homology -directed repair canbe used for gene correction, gene replacement, gene tagging, transgcnc insertion, nucleotide deletion, gene disruption, gene mutation, etc.

[0376] In one embodiment, the gene-editing protein is a CRISPR-associated nuclease. The native prokaryotic CRISPR-associated nuclease system comprises an array of short repeats with intervening variable sequences of constant length (i.e., clusters of regularly interspaced short palindromic repeats), and CRISPR-associated ("Cas") nuclease proteins. The RNA of the transcribed CRISPR array is processed by a subset of the Cas proteins into small guide RNAs, which generally have two components as discussed below. There are at least three different systems: Type I, Type II and Type III. The enzymes involved in the processing of the RNA into mature crRNA are different in the 3 systems. In the native prokaryotic system, the guide RNA ("gRNA") comprises two short, non-coding RNA species referred to as CRISPR RNA ("crRNA") and transacting RNA ("tracrRNA"). In an exemplary system, the gRNA forms a complex with a nuclease, for example, a Cas nuclease. The gRNA: nuclease complex binds a target polynucleotide sequence having a protospacer adjacent motif ("PAM") and a protospacer, which is a sequence complementary to a portion of the gRNA. The recognition and binding of the target polynucleotide by the gRNA: nuclease complex induces cleavage of the target.

[0377] Any CRISPR-associated nuclease can be used in the system and methods of the invention. CRISPR nuclease systems are known to those of skill in the art, e g. Cas9. Casl2, Casl2a, or the like, see Patents / applications 8,993,233. US 2015 / 0291965, US 2016 / 0175462, US 2015 / 0020223. US 2014 / 0179770, 8,697,359; 8,771.945; 8, 795,965; WO 2015 / 191693; US 8,889.418; WO 2015 / 089351; WO 2015 / 089486; WO 2016 / 028682; WO 2016 / 049258; WO 2016 / 094867; WO 2016 / 094872; WO 2016 / 094874; WO 2016 / 112242; US 2016 / 0153004; US 2015 / 0056705; US 2016 / 0090607; US 2016 / 0029604; 8,865,406; 8,871,445; each of which are incorporated by reference in their entirety. The nuclease can also be a phage Cas nuclease, e.g., CasO (e.g., Pausch et al. Science 369:333-7 (2020); which is incorporated by reference herein in its entirety).

[0378] The full-length guide nucleic acid strand can be any length. For example, the guide nucleic acid strand can be about or more than about 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29. 30, 35, 40, 45, 50, 75, or more nucleotides in length. In some embodiments of the various aspects described herein, a nucleic acid strand is less than about 75, 50, 45, 40, 35, 30, 25, 20, 15, 12. or fewer nucleotides in length. For example, the guide nucleic acid sequence is 10-30 nucleotides long.

[0379] In addition to a sequence that is complementary to a target nucleic acid, in some embodiments, the gNA also comprises a scaffold sequence. Expression of a gNA encoding both a sequence complementary to a target nucleic acid and scaffold sequence has the dual function of both binding (hybridizing) to the target nucleic acid and recruiting the endonuclease to the target nucleicacid, which may result in sitc-spccific CRISPR activity. In some embodiments, such a chimeric gNA may be referred to as a single guide RNA (sgRNA).

[0380] In some embodiments of the various aspects described herein, the guide nucleic acid is designed using a guide design tool (e.g., Benchling™; Broad Institute GPP™; CasOFFinder™; CHOPCHOP™; CRISPOR™; Deskgen™; E-CRISP™; Geneious™; GenHub™; GUIDES™ (e g., for library design); Horizon Discovery™; IDT™; Off-Spotter™; and Synthego™; which are available on the world wide web).

[0381] The term "vector", as used herein, refers to a nucleic acid construct designed for delivery to a host cell or for transfer between different host cells. As used herein, a vector can be viral or non- viral. The term “vector” encompasses any genetic element that is capable of replication when associated with the proper control elements and that can transfer gene sequences to cells. A vector can include, but is not limited to. a cloning vector, an expression vector, a recombinant vector, a plasmid, phage, transposon, cosmid, chromosome, virus, virion, etc.

[0382] As used herein, the term "expression vector" refers to a vector that directs expression of an RNA or polypeptide from sequences linked to transcriptional regulatory sequences on the vector. The sequences expressed will often, but not necessarily, be heterologous to the cell. An expression vector may comprise additional elements, for example, the expression vector may have two replication systems, thus allowing it to be maintained in two organisms, for example in human cells for expression and in a prokaryotic host for cloning and amplification. The term "expression" refers to the cellular processes involved in producing RNA and proteins and as appropriate, secreting proteins, including where applicable, but not limited to, for example, transcription, transcript processing, translation and protein folding, modification and processing. "Expression products" include RNA transcribed from a gene, and polypeptides obtained by translation of mRNA transcribed from a gene. The term "gene" means the nucleic acid sequence which is transcribed (DNA) to RNA in vitro or in vivo when operably linked to appropriate regulatory sequences. The gene may or may not include regions preceding and following the coding region, e.g. 5’ untranslated (5’UTR) or "leader" sequences and 3’ UTR or "trailer" sequences, as well as intervening sequences (introns) betw een individual coding segments (exons).

[0383] As used herein, the term “viral vector" refers to a nucleic acid vector construct that includes at least one element of viral origin and has the capacity to be packaged into a viral vector particle. The viral vector can contain the nucleic acid encoding a polypeptide as described herein in place of non-essential viral genes. The vector and / or particle may be utilized for the purpose of transferring any nucleic acids into cells either in vitro or in vivo. Numerous forms of viral vectors are known in the art.

[0384] By “recombinant vector” is meant a vector that includes a heterologous nucleic acid sequence, or "transgene” that is capable of expression in vivo. It should be understood that the vectorsdescribed herein can, in some embodiments, be combined with other suitable compositions and therapies. In some embodiments, the vector is episomal. The use of a suitable episomal vector provides a means of maintaining the nucleotide of interest in the subject in high copy number extra chromosomal DNA thereby eliminating potential effects of chromosomal integration.

[0385] As used herein, the terms "treat,” "treatment," "treating,” or “amelioration” refer to therapeutic treatments, wherein the object is to reverse, alleviate, ameliorate, inhibit, slow down or stop the progression or severity of a condition associated with a disease or disorder, e.g. a condition or disease described herein. The term “treating" includes reducing or alleviating at least one adverse effect or symptom of a condition, disease or disorder. Treatment is generally “effective" if one or more symptoms or clinical markers are reduced. Alternatively, treatment is “effective" if the progression of a disease is reduced or halted. That is, "treatment" includes not just the improvement of symptoms or markers, but also a cessation of. or at least slowing of, progress or worsening of symptoms compared to what would be expected in the absence of treatment. Beneficial or desired clinical results include, but are not limited to. alleviation of one or more symptom(s), diminishment of extent of disease, stabilized (z.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, remission (whether partial or total), and / or decreased mortality, whether detectable or undetectable. The term "treatment" of a disease also includes providing relief from the symptoms or side-effects of the disease (including palliative treatment).

[0386] As used herein, the term “pharmaceutical composition” refers to the active agent in combination with a pharmaceutically acceptable carrier e.g. a carrier commonly used in the pharmaceutical industry. The phrase "pharmaceutically acceptable" is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. In some embodiments of any of the aspects, a pharmaceutically acceptable carrier can be a carrier other than water. In some embodiments of any of the aspects, a pharmaceutically acceptable carrier can be a cream, emulsion, gel, liposome, nanoparticle, and / or ointment. In some embodiments of any of the aspects, a pharmaceutically acceptable carrier can be an artificial or engineered carrier, e.g., a carrier that the active ingredient would not be found to occur in in nature.

[0387] As used herein, the term "administering." refers to the placement of a compound as disclosed herein into a subject by a method or route which results in at least partial delivery of the agent at a desired site. Pharmaceutical compositions comprising the compounds disclosed herein can be administered by any appropriate route which results in an effective treatment in the subject.

[0388] As used herein, “contacting" refers to any suitable means for delivering, or exposing, an agent to at least one cell. Exemplary' delivery' methods include, but are not limited to, direct delivery to cell culture medium, perfusion, injection, or other delivery method well known to one skilled in the art. In some embodiments, contacting comprises phy sical human activity, e.g., an injection; an act of dispensing, mixing, and / or decanting; and / or manipulation of a delivery device or machine.

[0389] The term "effective amount" means an amount of a composition sufficient to provide at least some amelioration of the symptoms associated with the condition. In one embodiment, the "effective amount" means an amount of a composition would decrease the markers or symptoms of the condition in a subject having the condition.

[0390] The term "statistically significant" or “significantly" refers to statistical significance and generally means a two standard deviation (2SD) or greater difference.

[0391] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term “about.” The term “about” when used in connection with percentages can mean ±1%. In some embodiments of any of the aspects, about refers to a range within 1% of the indicated amount.

[0392] In some embodiments of any of the aspects, an amount, level, or concentration described herein is that amount H^10%. In some embodiments of any of the aspects, an amount, level, or concentration described herein is that amount +.5%. In some embodiments of any of the aspects, an amount, level, or concentration described herein is that amount ± 2%. In some embodiments of any of the aspects, an amount, level, or concentration described herein is that amoimt j^l%.

[0393] As used herein, the term "comprising" or "comprises" is used in reference to methods and compositions, and respective component(s) thereof, that are essential to the invention, yet open to the inclusion of unspecified elements, whether essential or not. As used herein, the term “comprising” means that other elements can also be present in addition to the defined elements presented. The use of “comprising” indicates inclusion rather than limitation.

[0394] The term "consisting of refers to compositions, methods, and respective components thereof as described herein, which are exclusive of any element not recited in that description of the embodiment.

[0395] As used herein the term "consisting essentially of refers to those elements required for a given embodiment. The term permits the presence of additional elements that do not materially affect the basic and novel or functional characteristic(s) of that embodiment of the invention.

[0396] As used herein, the term “specific binding” refers to a chemical interaction between two molecules, compounds, cells and / or particles wherein the first entity binds to the second, target entity with greater specificity and affinity than it binds to a third entity which is a non-target. In some embodiments, specific binding can refer to an affinity of the first entity for the second target entitywhich is at least 10 times, at least 50 times, at least 100 times, at least 500 times, at least 1000 times or greater than the affinity for the third nontarget entity. A reagent specific for a given target is one that exhibits specific binding for that target under the conditions of the assay being utilized.

[0397] The singular terms "a," "an," and "the" include plural referents unless context clearly indicates otherwise. Similarly, the word "or" is intended to include "and" unless the context clearly indicates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described below. The abbreviation, "e.g." is derived from the Latin exempli gratia, and is used herein to indicate a non-limiting example. Thus, the abbreviation "e.g." is synonymous with the term "for example."

[0398] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in. or deleted from, a group for reasons of convenience and / or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

[0399] Unless otherwise defined herein, scientific and technical terms used in connection with the present application shall have the meanings that are commonly understood by those of ordinary' skill in the art to which this disclosure belongs. It should be understood that this invention is not limited to the particular methodology7, protocols, and reagents, etc., described herein and as such can vary. The terminology7used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention, w7hich is defined solely by the claims. Definitions of common terms in immunology and molecular biology can be found in The Merck Manual of Diagnosis and Therapy, 19th Edition, published by Merck Sharp & Dohme Corp.. 2011 (ISBN 978-0-911910-19-3); Robert S. Porter et al. (eds.), The Encyclopedia of Molecular Cell Biology and Molecular Medicine, published by Blackwell Science Ltd., 1999-2012 (ISBN 9783527600908); and Robert A. Meyers (ed.), Molecular Biology' and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 1-56081-569-8); Immunology' by Werner Luttmann, published by Elsevier, 2006; laneway's Immunobiology, Kenneth Murphy, Allan Mowat, Casey Weaver (eds.), Taylor & Francis Limited, 2014 (ISBN 0815345305, 9780815345305); Lewin's Genes XI, published by Jones & Bartlett Publishers, 2014 (ISBN- 1449659055); Michael Richard Green and Joseph Sambrook, Molecular Cloning: A Laboratory Manual. 4thed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., USA (2012) (ISBN 1936113414); Davis et al., Basic Methods in Molecular Biology. Elsevier Science Publishing, Inc., New York, USA (2012) (ISBN 044460149X); Laboratory Methods in Enzymology: DNA, Jon Lorsch (ed.) Elsevier. 2013 (ISBN 0124199542); Current Protocols in Molecular Biology (CPMB), FrederickM. Ausubcl (cd.), John Wiley and Sons, 2014 (ISBN 047150338X, 9780471503385), Current Protocols in Protein Science (CPPS), John E. Coligan (ed.), John Wiley and Sons, Inc., 2005; and Current Protocols in Immunology (CPI) (John E. Coligan, ADA M Kruisbeek, David H Margulies, Ethan M Shevach, Warren Strobe, (eds.) John Wiley and Sons, Inc., 2003 (ISBN 0471142735, 9780471142737), the contents of which are all incorporated by reference herein in their entireties.

[0400] One of skill in the art can readily identify a chemotherapeutic agent of use (e.g. see Physicians' Cancer Chemotherapy Drug Manual 2014, Edward Chu, Vincent T. DeVita Jr., Jones & Bartlett Learning; Principles of Cancer Therapy, Chapter 85 in Harrison's Principles of Internal Medicine. 18th edition; Therapeutic Targeting of Cancer Cells: Era of Molecularly Targeted Agents and Cancer Pharmacology. Chs. 28-29 in Abeloff s Clinical Oncology, 2013 Elsevier; and Fischer D S (ed): The Cancer Chemotherapy Handbook. 4th ed. St. Louis, Mosby-Year Book, 2003).

[0401] Other terms are defined herein within the description of the various aspects of the invention.

[0402] All patents and other publications; including literature references, issued patents, published patent applications, and co-pending patent applications; cited throughout this application are expressly incorporated herein by reference for the purpose of describing and disclosing, for example, the methodologies described in such publications that might be used in connection with the technology described herein. These publications are provided solely for their disclosure prior to the filing date of the present application. Nothing in this regard should be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention or for any other reason. All statements as to the date or representation as to the contents of these documents is based on the information available to the applicants and does not constitute any admission as to the correctness of the dates or contents of these documents.

[0403] The description of embodiments of the disclosure is not intended to be exhaustive or to limit the disclosure to the precise form disclosed. While specific embodiments of. and examples for, the disclosure are described herein for illustrative purposes, various equivalent modifications are possible within the scope of the disclosure, as those skilled in the relevant art will recognize. For example, while method steps or functions are presented in a given order, alternative embodiments may perform functions in a different order, or functions may be performed substantially concurrently. The teachings of the disclosure provided herein can be applied to other procedures or methods as appropriate. The various embodiments described herein can be combined to provide further embodiments. Aspects of the disclosure can be modified, if necessary, to employ the compositions, functions and concepts of the above references and application to provide yet further embodiments of the disclosure. Moreover, due to biological functional equivalency considerations, some changes can be made in protein structure without affecting the biological or chemical action in kind or amount.These and other changes can be made to the disclosure in light of the detailed description. All such modifications are intended to be included within the scope of the appended claims.

[0404] Specific elements of any of the foregoing embodiments can be combined or substituted for elements in other embodiments. Furthermore, while advantages associated with certain embodiments of the disclosure have been described in the context of these embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the disclosure.

[0405] In some embodiments, the present technology may be defined in any of the following numbered paragraphs:1. A composition comprising at least one ionic liquid comprising: an anion which is selected from the group consisting of: hexenoic acid, pentenoic acid, hexanoic acid, methylpentenoic acid, butyric acid, heptanoic acid, dimethylacrylic acid (DMA A); a cation which is a quaternary ammonium.2. The composition of any one of the preceding paragraphs wherein the anion is selected from the group consisting of: hexenoic acid, hexanoic acid, methylpentenoic acid, and heptanoic acid.3. The composition of any one of the preceding paragraphs wherein the anion is selected from the group consisting of: hexanoic acid, methylpentenoic acid, and heptanoic acid.4. The composition of any one of the preceding paragraphs wherein the cation is choline or acetylcholine.5. The composition of any one of the preceding paragraphs wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid;Choline methy lpentenoic acid;Choline hexenoic acid;Acetylcholine hexanoic acid; and Methacholine hexenoic acid.6. The composition of any one of the preceding paragraphs wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a cation:anion ratio of 1 : 1 ;Choline heptanoic acid at a cation:anion ratio of 2: 1;Choline methylpentenoic acid at a catioiranion ratio of 1:2:Choline hexenoic acid at a cation:anion ratio of 1 :2;Acetylcholine hexanoic acid at a cation: anion ratio of 1 : 1 ; andMcthacholinc hcxcnoic acid at a cation: anion ratio of 1 : 1. The composition of any one of the preceding paragraphs wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid;Choline methylpentenoic acid;Choline hexenoic acid; andAcetylcholine hexanoic acid. The composition of any one of the preceding paragraphs wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a catiomanion ratio of 2: 1;Choline methylpentenoic acid at a catiomanion ratio of 1:2:Choline hexenoic acid at a catiomanion ratio of 1 :2; andAcetylcholine hexanoic acid at a cation: anion ratio of 1 : 1. The composition of any one of the preceding paragraphs wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid; andCholine methylpentenoic acid. The composition of any one of the preceding paragraphs wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a catiomanion ratio of 2:1; andCholine methylpentenoic acid at a catiomanion ratio of 1:2. The composition of any one of the preceding paragraphs wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid;Choline methylpentenoic acid;Choline hexenoic acid; andMethacholine hexenoic acid. The composition of any one of the preceding paragraphs wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a catiomanion ratio of 2: 1 ;Choline mcthylpcntcnoic acid at a catiomanion ratio of 1:2;Choline hexenoic acid at a catiomanion ratio of 1 :2; and Methacholine hexenoic acid at a cation: anion ratio of 1 : 1. The composition of any one of the preceding paragraphs wherein the ionic liquid is selected from tire group consisting of:Choline methylpentenoic acid; andCholine hexenoic acid. The composition of any one of the preceding paragraphs wherein the ionic liquid is selected from the group consisting of:Choline methylpentenoic acid at a catiomanion ratio of 1:2: andCholine hexenoic acid at a catiomanion ratio of 1 :2. The composition of any one of the preceding paragraphs wherein the ionic liquid is Choline hexanoic acid. The composition of any one of the preceding paragraphs wherein the ionic liquid is Choline heptanoic acid. The composition of any one of the preceding paragraphs wherein the ionic liquid is Choline methylpentenoic acid. The composition of any one of the preceding paragraphs wherein the ionic liquid is Choline hexenoic acid. The composition of any one of the preceding paragraphs wherein the ionic liquid is Acetylcholine hexanoic acid. The composition of any one of the preceding paragraphs wherein the ionic liquid is Methacholine hexenoic acid. The composition of any one of the preceding paragraphs wherein the ionic liquid is Choline hexanoic acid at a catiomanion ratio of 1 : 1. The composition of any one of the preceding paragraphs wherein the ionic liquid is Choline heptanoic acid at a catiomanion ratio of 2: 1. The composition of any one of the preceding paragraphs wherein the ionic liquid is Choline methylpentenoic acid at a catiomanion ratio of 1:2. The composition of any one of the preceding paragraphs wherein the ionic liquid is Choline hexenoic acid at a catiomanion ratio of 1:2. The composition of any one of the preceding paragraphs wherein the ionic liquid is Acetylcholine hexanoic acid at a catiomanion ratio of 1 : 1. The composition of any one of the preceding paragraphs wherein the ionic liquid is Methacholine hexenoic acid at a catiomanion ratio of 1 : 1.The composition of any one of the preceding paragraphs, wherein the quaternary ammonium comprises an e...

Claims

What is claimed herein is:

1. A composition comprising at least one ionic liquid comprising: an anion which is selected from the group consisting of: hexenoic acid, pentenoic acid, hexanoic acid, methylpentenoic acid, butyric acid, heptanoic acid, dimethylacrylic acid (DMA A); lactic acid; glycolic acid; gluconic acid; glutaric acid; tartaric acid; citric acid; and EDTA; a cation which is a quaternary ammonium.

2. The composition of any one of the preceding claims wherein the anion is selected from the group consisting of: hexenoic acid, hexanoic acid, methylpentenoic acid, and heptanoic acid.

3. The composition of any one of the preceding claims wherein the anion is selected from the group consisting of: hexanoic acid, methylpentenoic acid, and heptanoic acid.

4. The composition of any one of the preceding claims wherein the cation is choline or acetylcholine.

5. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid;Choline methylpentenoic acid;Choline hexenoic acid;Acetylcholine hexanoic acid; andMethacholine hexenoic acid.

6. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a catiomanion ratio of 2: 1;Choline methylpentenoic acid at a catiomanion ratio of 1:2:Choline hexenoic acid at a catiomanion ratio of 1 :2;Acetylcholine hexanoic acid at a cation: anion ratio of 1 : 1 ; andMethacholine hexenoic acid at a cation: anion ratio of 1 : 1.

7. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid;Choline methylpentenoic acid;Choline hexenoic acid; andAcetylcholine hexanoic acid.

8. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a cation: anion ratio of 2 : 1 ;Choline methylpentenoic acid at a catiomanion ratio of 1:2:Choline hexenoic acid at a catiomanion ratio of 1 :2; andAcetylcholine hexanoic acid at a cation: anion ratio of 1 : 1.

9. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid; andCholine methylpentenoic acid.

10. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1:1;Choline heptanoic acid at a catiomanion ratio of 2: 1; andCholine methylpentenoic acid at a catiomanion ratio of 1 :2.

11. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline heptanoic acid;Choline methylpentenoic acid;Choline hexenoic acid; andMethacholine hexenoic acid.

12. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline heptanoic acid at a catiomanion ratio of 2:1;Choline methylpentenoic acid at a catiomanion ratio of 1:2:Choline hexenoic acid at a catiomanion ratio of 1 :2; andMethacholine hexenoic acid at a cation: anion ratio of 1 : 1.

13. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline methylpentenoic acid; andCholine hexenoic acid.

14. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline methylpentenoic acid at a catiomanion ratio of 1:2; andCholine hexenoic acid at a catiomanion ratio of 1 :2.

15. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid;Choline methylpentenoic acid; andCholine hexenoic acid.

16. The composition of any one of the preceding claims wherein the ionic liquid is selected from the group consisting of:Choline hexanoic acid at a catiomanion ratio of 1 : 1 ;Choline methylpentenoic acid at a catiomanion ratio of 1:2: andCholine hexenoic acid at a catiomanion ratio of 1 :2.

17. The composition of any one of the preceding claims wherein the ionic liquid is Choline hexanoic acid.

18. The composition of any one of the preceding claims wherein the ionic liquid is Choline heptanoic acid.

19. The composition of any one of the preceding claims wherein the ionic liquid is Choline methylpentenoic acid.

20. The composition of any one of the preceding claims wherein the ionic liquid is Choline hexenoic acid.

21. The composition of any one of the preceding claims wherein the ionic liquid is Acetylcholine hexanoic acid.

22. The composition of any one of the preceding claims wherein the ionic liquid is Methacholine hexenoic acid.

23. The composition of any one of the preceding claims wherein the ionic liquid is Choline hexanoic acid at a catiomanion ratio of 1 : 1.

24. The composition of any one of the preceding claims wherein the ionic liquid is Choline heptanoic acid at a catiomanion ratio of 2: 1.

25. The composition of any one of the preceding claims wherein the ionic liquid is Choline methylpentenoic acid at a catiomanion ratio of 1:2.

26. The composition of any one of the preceding claims wherein the ionic liquid is Choline hexenoic acid at a catiomanion ratio of 1:2.

27. The composition of any one of the preceding claims wherein the ionic liquid is Acetylcholine hexanoic acid at a catiomanion ratio of 1 : 1.

28. The composition of any one of the preceding claims wherein the ionic liquid is Mcthacholinc hexenoic acid at a catiomanion ratio of 1 : 1.

29. The composition of claim 1, wherein the anion is selected from the group consisting of: lactic acid; glycolic acid; gluconic acid; glutaric acid; tartaric acid; citric acid; and EDTA.

30. The composition of claim 1, wherein the anion is selected from the group consisting of: glutaric acid and EDTA.

31. The composition of any one of the preceding claims, wherein the quaternary ammonium comprises an ester group.

32. The composition of any one of the preceding claims, wherein the cation is choline, acetylcholine, or methacholine.

33. The composition of any one of the preceding claims, wherein the cation is choline.

34. The composition of any one of the preceding claims, wherein die ionic liquid comprises a ratio of cation to anion of from about 2: 1 to about 1:2.

35. The composition of any one of the preceding claims, wherein die ionic liquid comprises a ratio of cation to anion of from about 2: 1 to about 1:1.

36. The composition of any one of the preceding claims, wherein die ionic liquid comprises a ratio of cation to anion of about 2:1.

37. The composition of any one of the preceding claims, wherein die ionic liquid comprises a ratio of cation to anion of about 1:1.

38. The composition of any one of the preceding claims, wherein die ionic liquid has a cation: anion ratio of less than 1:1.

39. The composition of any one of the preceding claims, wherein die ionic liquid has a cation: anion ratio with an excess of cation.

40. The composition of any one of the preceding claims, further comprising at least a second ionic liquid.

41. The composition of claim 40. wherein the at least one ionic liquid and the second ionic liquid each comprise a different anion.

42. The composition of any one of the preceding claims, further comprising at least one active compound in combination with the at least one ionic liquid.

43. The composition of claim 42, wherein the active compound is present at a concentration of at least 100 mg / mL.

44. The composition of claim 42, wherein the active compound is present at a concentration of at least 150 mg / mL.

45. The composition of claim 42, wherein the active compound is present at a concentration of at least 200 mg / mL.

46. The composition of claim 42, wherein the active compound is present at a concentration of at least 300 mg / mL.

47. The composition of any one of claims 42-46, wherein the active compound comprises a polypeptide.

48. The composition of claim 47. wherein the polypeptide is an antibody or antibody reagent.

49. The composition of any one of claims 40-48, wherein the active compound has a molecular weight of greater than 450.

50. The composition of any one of claims 40-48, wherein the active compound has a molecular weight of greater than 500.

51. The composition of any one of the preceding claims, wherein the ionic liquid is at a concentration of from about 1 to about 10%v / v.

52. The composition of any one of the preceding claims, wherein the ionic liquid is at a concentration of at least l%v / v.

53. The composition of any one of the preceding claims, wherein tire ionic liquid is at a concentration of less than 20%v / v.

54. The composition of any one of the preceding claims, wherein tire ionic liquid is at a concentration of less than 10%v / v.

55. The composition of any one of the preceding claims, wherein tire ionic liquid is at a concentration of from about 1 to about 5%v / v.

56. The composition of any one of the preceding claims, wherein tire ionic liquid is at a concentration of at least 0. l%w / v.

57. The composition of any one of the preceding claims, wherein die ionic liquid is at a concentration of from about 10 to about 70%w / v.

58. The composition of any one of the preceding claims, wherein the ionic liquid is at a concentration of from about 30 to about 50%w / v.

59. The composition of any one of the preceding claims, wherein the ionic liquid is at a concentration of from about 30 to about 40%w / v.

60. The composition of any one of the preceding claims, wherein the ionic liquid is at a concentration of less than 10%w / v.

61. The composition of any one of the preceding claims, wherein the composition has a viscosity' of less than 20 cP.

62. The composition of any one of the preceding claims, wherein the composition has a viscosity of 1 cP to 20 cP.

63. The composition of any one of the preceding claims, wherein the composition is formulated for administration transdermally subcutaneously, intradermally, or parenterally.

64. The composition of claim 63, wherein the composition is formulated for subcutaneous administration.

65. The composition of claim 63, wherein the composition is formulated for transdermal administration.

66. The composition of any one of the preceding claims, further comprising at least one non-ionic surfactant.

67. The composition of any one of the preceding claims, further comprising a pharmaceutically acceptable carrier.

68. The composition of any one of the preceding claims, wherein tire composition is an admixture.

69. The composition of any one of the preceding claims, wherein tire composition is provided in one or more nanoparticlcs.

70. The composition of any one of the preceding claims, comprising one or more nanoparticles comprising the active compound, the nanoparticles in solution or suspension in a composition comprising the ionic liquid.

71. A method of administering at least one active compound to a subject, the method comprising administering a composition of any one of claims 1-62.

72. The method of claim 71, wherein the composition is administered once.

73. The method of any one of claims 71-72. wherein the composition is administered in multiple doses.

74. The method of any one of claims 71-73. wherein the administering is transdermally, subcutaneously, intradermally, or parenterally.

75. The method of any one of claims 71-74. wherein the administering is subcutaneous.

76. A composition of any one of claims 1-62 for use in a method of administering at least one active compound to a subject.

77. A composition of any one of claims 1-62 for use in a method of stabilizing at least one active compound.

78. A composition of any one of claims 1-62 for use in a method of solubilizing at least one active compound.

79. A composition of any one of claims 1-62 for use in a method of increasing the bioavailabilitv of at least one active compound.

80. A composition of any one of claims 1-62 for use in a method of providing a high concentration formulation of at least one active compound.

81. A composition of any one of claims 1-62 for use in a method of providing a high concentration, injectable viscosity fonnulation of at least one active compound.

82. The composition of claim 76-81, wherein the composition is administered once.

83. The composition of any one of claims 76-82, wherein the composition is administered in multiple doses.

84. The composition of any one of claims 76-83, wherein the administering is transdermally. subcutaneously, intradermally, or parenterally.

85. The composition of any one of claims 76-84, wherein the administering is subcutaneous.

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