Methyl-branched liposomes for sustained drug delivery

Abstract

The present disclosure provides compositions comprising a liposome encapsulating a therapeutic agent or a diagnostic agent. The liposome comprises a lipid having a branched molecular structure (i.e., a lipid of Formula (I)). The compositions thus provide a means of controlled and prolonged delivery of therapeutic and diagnostic agents. The present disclosure further provides kits comprising the compositions, methods of treating or preventing a disease or disorder, and methods of preparing the compositions.

Description

[0001]METHYL-BRANCHED LIPOSOMES FOR SUSTAINED DRUG DELIVERY RELATED APPLICATIONS This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application, U.S.S.N.63 / 587,275, filed October 2, 2023, which is incorporated herein by reference in its entirety. FEDERALLY SPONSORED RESEARCH This invention was made with government support under Grant Number GM131728, awarded by the National Institutes of Health. The Government has certain rights in the invention. BACKGROUND Since first reported in the 1960s, liposomes have been extensively investigated for drug delivery applications. The size of liposomes can range from 40 nm – 30 µm in diameter and they can be administered either systemically or locally. Liposome products have been used clinically for the treatment of a variety of indications. Despite this success, a major challenge in liposomal research is to minimize the uncontrolled leakage of payloads, which may lead to waste of therapeutics and systemic or local toxicity. Inadequate drug loading and control of payload leakage limit the duration of effect of liposomal drug carriers and can cause toxicity. SUMMARY The present disclosure stems from the recognition that lipid composition greatly affects the stability and permeability of liposomes, and that incorporating various natural or synthetic lipids into liposomes provides control of the stability and permeability of liposomes. Archaeal membranes are very stable and have low permeability to protons and other solutes, partially due to the presence of multiple branching methyl groups in the hydrocarbon chains of their lipid bilayer phospholipids. The methyl groups in archaeal lipids are believed to create a more rigid and tightly packed structure compared to the straight-chain fatty acids found in bacterial and eukaryotic membranes. This results in a higher degree of packing density in the lipid layers, which decreases the permeability of membranes. 11760147.1 As such, disclosed herein is a strategy wherein branched ester phospholipids are incorporated into liposomes to create drug delivery vehicles that encapsulate and release therapeutic agents in a sustained manner. In one aspect, disclosed herein is a composition comprising a liposome encapsulating a therapeutic agent or a diagnostic agent, wherein the liposome comprises a lipid of Formula (I): or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, wherein: m is an integer of 0-12; n is an integer of 0-12; x is an integer of 0-6; y is an integer of 0-6; R1is a phosphoglycerol, phosphocholine, phosphoethanolamine, phosphoinositol, or phosphoserine moiety; each R2is independently hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, -ORD1, -N(RD1a)2, -SRD1, -SO2, -NO2, -N3, or -CN, wherein at least one instance of R2is not hydrogen; each R3is independently hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, -ORD1, -N(RD1a)2, -SRD1, -SO2, -NO2, -N3, or -CN, wherein at least one instance of R3is not hydrogen; X1is substituted or unsubstituted C1-6 alkylene; X2is substituted or unsubstituted C1-6alkylene; wherein each RD1is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkynyl group, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted 11760147.1 aryl, optionally substituted heteroaryl, or an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and wherein each RD1ais independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted linear alkynyl, optionally substituted cycloalkynyl group, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two instances of RD1aare taken together with their intervening atoms to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring. In another aspect, provided are methods of treating a disease or condition, the method comprising administering an effective amount of the composition. In another aspect, provided are kits comprising the composition and instructions for using the composition. The details of certain embodiments of the invention are set forth in the Detailed Description of Certain Embodiments, as described below. Other features, objects, and advantages of the invention will be apparent from the Definitions, Drawings, Examples, and Claims. DEFINITIONS Definitions of specific functional groups and chemical terms are described in more detail below. The chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75thEd., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Thomas Sorrell, Organic Chemistry, University Science Books, Sausalito, 1999;Michael B. Smith, March’s Advanced Organic Chemistry, 7thEdition, John Wiley & Sons, Inc., New York, 2013; Richard C. Larock, Comprehensive Organic Transformations, John Wiley & Sons, Inc., New York, 2018; and Carruthers, Some Modern Methods of Organic Synthesis, 3rdEdition, Cambridge University Press, Cambridge, 1987. Compounds described herein can comprise one or more asymmetric centers, and thus can exist in various stereoisomeric forms, e.g., enantiomers and / or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer, or 11760147.1 geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, E.L. Stereochemistry of Carbon Compounds (McGraw–Hill, NY, 1962); and Wilen, S.H., Tables of Resolving Agents and Optical Resolutions p.268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972). The disclosure additionally encompasses compounds as individual isomers substantially free of other isomers, and alternatively, as mixtures of various isomers. When a range of values is listed, it is intended to encompass each value and sub–range within the range. For example, “C1–6” is intended to encompass C1, C2, C3, C4, C5, C6, C1–6, C1–5, C1–4, C1–3, C1–2, C2–6, C2–5, C2–4, C2–3, C3–6, C3–5, C3–4, C4–6, C4–5, and C5–6. For example, “C1-6alkyl” encompasses, C1, C2, C3, C4, C5, C6, C1–6, C1–5, C1–4, C1–3, C1–2, C2–6, C2–5, C2–4, C2–3, C3– 6, C3–5, C3–4, C4–6, C4–5, and C5–6 alkyl. The term “alkyl” refers to a radical of a straight-chain or branched saturated hydrocarbon group having from 1 to 20 carbon atoms (“C1–20 alkyl”). The term “branched alkyl” refers to a radical of a branched saturated hydrocarbon group having from 1 to 20 carbon atoms (“branched C1–20alkyl”), for example, isopropyl, t-butyl, sec-butyl, iso-butyl, neopentyl, isopentyl, and neoheptyl. The term “unbranched alkyl” is the same as a straight-chain or linear alkyl group, i.e., an alkyl group having no alkyl branching groups. In some embodiments, an alkyl group has 1 to 12 carbon atoms (“C1–12alkyl”). In some embodiments, an alkyl group has 1 to 10 carbon atoms (“C1–10alkyl”). In some embodiments, an alkyl group has 1 to 9 carbon atoms (“C1–9alkyl”). In some embodiments, an alkyl group has 1 to 8 carbon atoms (“C1–8 alkyl”). In some embodiments, an alkyl group has 1 to 7 carbon atoms (“C1–7 alkyl”). In some embodiments, an alkyl group has 1 to 6 carbon atoms (“C1–6alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“C1–5 alkyl”). In some embodiments, an alkyl group has 1 to 4 carbon atoms (“C1–4 alkyl”). In some embodiments, an alkyl group has 1 to 3 carbon atoms (“C1–3 alkyl”). In some embodiments, an alkyl group has 1 to 2 carbon atoms (“C1–2alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“C1 alkyl”). In some embodiments, an alkyl group has 2 to 6 carbon atoms (“C2-6 alkyl”). Examples of C1–6 alkyl groups include methyl (C1), 11760147.1 ethyl (C2), propyl (C3) (e.g., n-propyl, isopropyl), butyl (C4) (e.g., n-butyl, tert-butyl, sec-butyl, isobutyl), pentyl (C5) (e.g., n-pentyl, 3-pentanyl, amyl, neopentyl, 3-methyl-2-butanyl, tert- amyl), and hexyl (C6) (e.g., n-hexyl). Additional examples of alkyl groups include n-heptyl (C7), n-octyl (C8), n-dodecyl (C12), and the like. Unless otherwise specified, each instance of an alkyl group is independently unsubstituted (an “unsubstituted alkyl”) or substituted (a “substituted alkyl”) with one or more substituents (e.g., halogen, such as F). In certain embodiments, the alkyl group is an unsubstituted C1–12alkyl (such as unsubstituted C1–6alkyl, e.g., −CH3(Me), unsubstituted ethyl (Et), unsubstituted propyl (Pr, e.g., unsubstituted n-propyl (n-Pr), unsubstituted isopropyl (i-Pr)), unsubstituted butyl (Bu, e.g., unsubstituted n-butyl (n-Bu), unsubstituted tert-butyl (tert-Bu or t-Bu), unsubstituted sec-butyl (sec-Bu or s-Bu), unsubstituted isobutyl (i-Bu)). In certain embodiments, the alkyl group is a substituted C1–12alkyl (such as substituted C1–6 alkyl, e.g., –CH2F, –CHF2, –CF3, –CH2CH2F, –CH2CHF2, –CH2CF3, or benzyl (Bn)). The term “alkenyl” refers to a radical of a straight-chain or branched hydrocarbon group having from 1 to 20 carbon atoms and one or more carbon-carbon double bonds (e.g., 1, 2, 3, or 4 double bonds). In some embodiments, an alkenyl group has 1 to 20 carbon atoms (“C1-20 alkenyl”). In some embodiments, an alkenyl group has 1 to 12 carbon atoms (“C1–12alkenyl”). In some embodiments, an alkenyl group has 1 to 11 carbon atoms (“C1–11 alkenyl”). In some embodiments, an alkenyl group has 1 to 10 carbon atoms (“C1–10 alkenyl”). In some embodiments, an alkenyl group has 1 to 9 carbon atoms (“C1–9alkenyl”). In some embodiments, an alkenyl group has 1 to 8 carbon atoms (“C1–8alkenyl”). In some embodiments, an alkenyl group has 1 to 7 carbon atoms (“C1–7 alkenyl”). In some embodiments, an alkenyl group has 1 to 6 carbon atoms (“C1–6alkenyl”). In some embodiments, an alkenyl group has 1 to 5 carbon atoms (“C1–5alkenyl”). In some embodiments, an alkenyl group has 1 to 4 carbon atoms (“C1–4alkenyl”). In some embodiments, an alkenyl group has 1 to 3 carbon atoms (“C1–3 alkenyl”). In some embodiments, an alkenyl group has 1 to 2 carbon atoms (“C1–2 alkenyl”). In some embodiments, an alkenyl group has 1 carbon atom (“C1alkenyl”). The one or more carbon- carbon double bonds can be internal (such as in 2-butenyl) or terminal (such as in 1-butenyl). Examples of C1–4 alkenyl groups include methylidenyl (C1), ethenyl (C2), 1-propenyl (C3), 2- propenyl (C3), 1-butenyl (C4), 2-butenyl (C4), butadienyl (C4), and the like. Examples of C1–6alkenyl groups include the aforementioned C2-4 alkenyl groups as well as pentenyl (C5), pentadienyl (C5), hexenyl (C6), and the like. Additional examples of alkenyl include heptenyl 11760147.1 (C7), octenyl (C8), octatrienyl (C8), and the like. Unless otherwise specified, each instance of an alkenyl group is independently unsubstituted (an “unsubstituted alkenyl”) or substituted (a “substituted alkenyl”) with one or more substituents. In certain embodiments, the alkenyl group is an unsubstituted C1-20alkenyl. In certain embodiments, the alkenyl group is a substituted C1-20alkenyl. In an alkenyl group, a C=C double bond for which the stereochemistry is not specified -configuration. The term “alkynyl” refers to a radical of a straight-chain or branched hydrocarbon group having from 1 to 20 carbon atoms and one or more carbon-carbon triple bonds (e.g., 1, 2, 3, or 4 triple bonds) (“C1-20 alkynyl”). The term “linear alkynyl” refers to a radical of a straight-chain, unbranched hydrocarbon group having from 1 to 20 carbon atoms and one or more carbon- carbon triple bonds (e.g., 1, 2, 3, or 4 triple bonds) (“C1-20alkynyl”). In some embodiments, an alkynyl group has 1 to 10 carbon atoms (“C1-10alkynyl”). In some embodiments, an alkynyl group has 1 to 9 carbon atoms (“C1-9 alkynyl”). In some embodiments, an alkynyl group has 1 to 8 carbon atoms (“C1-8alkynyl”). In some embodiments, an alkynyl group has 1 to 7 carbon atoms (“C1-7alkynyl”). In some embodiments, an alkynyl group has 1 to 6 carbon atoms (“C1-6alkynyl”). In some embodiments, an alkynyl group has 1 to 5 carbon atoms (“C1-5 alkynyl”). In some embodiments, an alkynyl group has 1 to 4 carbon atoms (“C1-4 alkynyl”). In some embodiments, an alkynyl group has 1 to 3 carbon atoms (“C1-3alkynyl”). In some embodiments, an alkynyl group has 1 to 2 carbon atoms (“C1-2 alkynyl”). In some embodiments, an alkynyl group has 2 to 10 carbon atoms (“C2–10 alkynyl”). In some embodiments, an alkynyl group has 2 to 9 carbon atoms (“C2–9alkynyl”). In some embodiments, an alkynyl group has 2 to 8 carbon atoms (“C2–8 alkynyl”). In some embodiments, an alkynyl group has 2 to 7 carbon atoms (“C2–7 alkynyl”). In some embodiments, an alkynyl group has 2 to 6 carbon atoms (“C2–6 alkynyl”). In some embodiments, an alkynyl group has 2 to 5 carbon atoms (“C2–5alkynyl”). In some embodiments, an alkynyl group has 2 to 4 carbon atoms (“C2–4alkynyl”). In some embodiments, an alkynyl group has 2 to 3 carbon atoms (“C2–3 alkynyl”). In some embodiments, an alkynyl group has 2 carbon atoms (“C2 alkynyl”). In some embodiments, an alkynyl group has 1 carbon atom (“C1alkynyl”). The one or more carbon-carbon triple bonds can be internal (such as in 2- butynyl) or terminal (such as in 1-butynyl). Examples of C1-4 alkynyl groups include, without limitation, methylidynyl (C1), ethynyl (C2), 1-propynyl (C3), 2-propynyl (C3), 1-butynyl (C4), 2- butynyl (C4), and the like. Examples of C1-6alkenyl groups include the aforementioned C2-4alkynyl groups as well as pentynyl (C5), hexynyl (C6), and the like. Examples of C2–4 alkynyl 11760147.1 groups include, without limitation, ethynyl (C2), 1–propynyl (C3), 2–propynyl (C3), 1–butynyl (C4), 2–butynyl (C4), and the like. Examples of C2–6 alkenyl groups include the aforementioned C2–4alkynyl groups as well as pentynyl (C5), hexynyl (C6), and the like. Additional examples of alkynyl include heptynyl (C7), octynyl (C8), and the like. Unless otherwise specified, each instance of an alkynyl group is independently unsubstituted (an “unsubstituted alkynyl”) or substituted (a “substituted alkynyl”) with one or more substituents. In certain embodiments, the alkynyl group is an unsubstituted C1-20alkynyl. In certain embodiments, the alkynyl group is a substituted C1-20 alkynyl. In certain embodiments, the alkynyl group is an optionally substituted C2-20 alkynyl. The term “carbocyclyl” or “carbocyclic” refers to a radical of a non-aromatic cyclic hydrocarbon group having from 3 to 14 ring carbon atoms (“C3-14carbocyclyl”) and zero heteroatoms in the non-aromatic ring system. In some embodiments, a carbocyclyl group has 3 to 14 ring carbon atoms (“C3-14carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 13 ring carbon atoms (“C3-13carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 12 ring carbon atoms (“C3-12 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 11 ring carbon atoms (“C3-11 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 10 ring carbon atoms (“C3-10carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 8 ring carbon atoms (“C3-8 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 7 ring carbon atoms (“C3-7 carbocyclyl”). In some embodiments, a carbocyclyl group has 3 to 6 ring carbon atoms (“C3-6carbocyclyl”). In some embodiments, a carbocyclyl group has 4 to 6 ring carbon atoms (“C4-6carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 6 ring carbon atoms (“C5-6 carbocyclyl”). In some embodiments, a carbocyclyl group has 5 to 10 ring carbon atoms (“C5-10carbocyclyl”). Exemplary C3-6carbocyclyl groups include cyclopropyl (C3), cyclopropenyl (C3), cyclobutyl (C4), cyclobutenyl (C4), cyclopentyl (C5), cyclopentenyl (C5), cyclohexyl (C6), cyclohexenyl (C6), cyclohexadienyl (C6), and the like. Exemplary C3-8 carbocyclyl groups include the aforementioned C3-6 carbocyclyl groups as well as cycloheptyl (C7), cycloheptenyl (C7), cycloheptadienyl (C7), cycloheptatrienyl (C7), cyclooctyl (C8), cyclooctenyl (C8), bicyclo[2.2.1]heptanyl (C7), bicyclo[2.2.2]octanyl (C8), and the like. Exemplary C3-10 carbocyclyl groups include the aforementioned C3-8 carbocyclyl groups as well as cyclononyl (C9), cyclononenyl (C9), cyclodecyl (C10), cyclodecenyl (C10), octahydro-1H- indenyl (C9), decahydronaphthalenyl (C10), spiro[4.5]decanyl (C10), and the like. Exemplary C3-8 carbocyclyl groups include the aforementioned C3-10 carbocyclyl groups as well as cycloundecyl 11760147.1 (C11), spiro[5.5]undecanyl (C11), cyclododecyl (C12), cyclododecenyl (C12), cyclotridecane (C13), cyclotetradecane (C14), and the like. As the foregoing examples illustrate, in certain embodiments, the carbocyclyl group is either monocyclic (“monocyclic carbocyclyl”) or polycyclic (e.g., containing a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic carbocyclyl”) or tricyclic system (“tricyclic carbocyclyl”)) and can be saturated or can contain one or more carbon-carbon double or triple bonds. “Carbocyclyl” also includes ring systems wherein the carbocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups wherein the point of attachment is on the carbocyclyl ring, and in such instances, the number of carbons continue to designate the number of carbons in the carbocyclic ring system. Unless otherwise specified, each instance of a carbocyclyl group is independently unsubstituted (an “unsubstituted carbocyclyl”) or substituted (a “substituted carbocyclyl”) with one or more substituents. In certain embodiments, the carbocyclyl group is an unsubstituted C3-14 carbocyclyl. In certain embodiments, the carbocyclyl group is a substituted C3-14carbocyclyl. In some embodiments, “carbocyclyl” is a monocyclic, saturated carbocyclyl group having from 3 to 14 ring carbon atoms (“C3-14 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 10 ring carbon atoms (“C3-10 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms (“C3-8cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms (“C3-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 4 to 6 ring carbon atoms (“C4-6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 6 ring carbon atoms (“C5-6cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 10 ring carbon atoms (“C5-10cycloalkyl”). Examples of C5-6cycloalkyl groups include cyclopentyl (C5) and cyclohexyl (C5). Examples of C3-6 cycloalkyl groups include the aforementioned C5-6cycloalkyl groups as well as cyclopropyl (C3) and cyclobutyl (C4). Examples of C3-8cycloalkyl groups include the aforementioned C3-6cycloalkyl groups as well as cycloheptyl (C7) and cyclooctyl (C8). Unless otherwise specified, each instance of a cycloalkyl group is independently unsubstituted (an “unsubstituted cycloalkyl”) or substituted (a “substituted cycloalkyl”) with one or more substituents. In certain embodiments, the cycloalkyl group is an unsubstituted C3-14 cycloalkyl. In certain embodiments, the cycloalkyl group is a substituted C3-14 cycloalkyl. In certain embodiments, the carbocyclyl includes 0, 1, or 2 C=C double bonds in the carbocyclic ring system, as valency permits. The term “heterocyclyl” or “heterocyclic” refers to a radical of a 3- to 14-membered non- aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each 11760147.1 heteroatom is independently selected from nitrogen, oxygen, and sulfur (“3–14 membered heterocyclyl”). In heterocyclyl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. A heterocyclyl group can either be monocyclic (“monocyclic heterocyclyl”) or polycyclic (e.g., a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic heterocyclyl”) or tricyclic system (“tricyclic heterocyclyl”)), and can be saturated or can contain one or more carbon-carbon double or triple bonds. Heterocyclyl polycyclic ring systems can include one or more heteroatoms in one or both rings. “Heterocyclyl” also includes ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more carbocyclyl groups wherein the point of attachment is either on the carbocyclyl or heterocyclyl ring, or ring systems wherein the heterocyclyl ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclyl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heterocyclyl ring system. Unless otherwise specified, each instance of heterocyclyl is independently unsubstituted (an “unsubstituted heterocyclyl”) or substituted (a “substituted heterocyclyl”) with one or more substituents. In certain embodiments, the heterocyclyl group is an unsubstituted 3–14 membered heterocyclyl. In certain embodiments, the heterocyclyl group is a substituted 3–14 membered heterocyclyl. In certain embodiments, the heterocyclyl is substituted or unsubstituted, 3- to 7-membered, monocyclic heterocyclyl, wherein 1, 2, or 3 atoms in the heterocyclic ring system are independently oxygen, nitrogen, or sulfur, as valency permits. In some embodiments, a heterocyclyl group is a 5–10 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–10 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–8 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–8 membered heterocyclyl”). In some embodiments, a heterocyclyl group is a 5–6 membered non-aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5–6 membered heterocyclyl”). In some embodiments, the 5–6 membered heterocyclyl has 1–3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has 1–2 ring heteroatoms selected from nitrogen, 11760147.1 oxygen, and sulfur. In some embodiments, the 5–6 membered heterocyclyl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Exemplary 3-membered heterocyclyl groups containing 1 heteroatom include azirdinyl, oxiranyl, and thiiranyl. Exemplary 4-membered heterocyclyl groups containing 1 heteroatom include azetidinyl, oxetanyl, and thietanyl. Exemplary 5-membered heterocyclyl groups containing 1 heteroatom include tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, and pyrrolyl-2,5-dione. Exemplary 5- membered heterocyclyl groups containing 2 heteroatoms include dioxolanyl, oxathiolanyl and dithiolanyl. Exemplary 5-membered heterocyclyl groups containing 3 heteroatoms include triazolinyl, oxadiazolinyl, and thiadiazolinyl. Exemplary 6-membered heterocyclyl groups containing 1 heteroatom include piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl. Exemplary 6-membered heterocyclyl groups containing 2 heteroatoms include piperazinyl, morpholinyl, dithianyl, and dioxanyl. Exemplary 6-membered heterocyclyl groups containing 3 heteroatoms include triazinyl. Exemplary 7-membered heterocyclyl groups containing 1 heteroatom include azepanyl, oxepanyl, and thiepanyl. Exemplary 8-membered heterocyclyl groups containing 1 heteroatom include azocanyl, oxecanyl and thiocanyl. Exemplary bicyclic heterocyclyl groups include indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, tetrahydrobenzothienyl, tetrahydrobenzofuranyl, tetrahydroindolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, decahydroisoquinolinyl, octahydrochromenyl, octahydroisochromenyl, decahydronaphthyridinyl, decahydro-1,8-naphthyridinyl, octahydropyrrolo[3,2-b]pyrrole, indolinyl, phthalimidyl, naphthalimidyl, chromanyl, chromenyl, 1H-benzo[e][1,4]diazepinyl, 1,4,5,7-tetrahydropyrano[3,4-b]pyrrolyl, 5,6-dihydro-4H-furo[3,2- b]pyrrolyl, 6,7-dihydro-5H-furo[3,2-b]pyranyl, 5,7-dihydro-4H-thieno[2,3-c]pyranyl, 2,3- dihydro-1H-pyrrolo[2,3-b]pyridinyl, 2,3-dihydrofuro[2,3-b]pyridinyl, 4,5,6,7-tetrahydro-1H- pyrrolo[2,3-b]pyridinyl, 4,5,6,7-tetrahydrofuro[3,2-c]pyridinyl, 4,5,6,7-tetrahydrothieno[3,2- b]pyridinyl, 1,2,3,4-tetrahydro-1,6-naphthyridinyl, and the like. The term “aryl” refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 pi electrons shared in a cyclic array) having 6–14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system (“C6-14aryl”). In some embodiments, an aryl group has 6 ring carbon atoms (“C6aryl”; e.g., phenyl). In some embodiments, an aryl group has 10 ring carbon atoms (“C10 aryl”; e.g., naphthyl such as 1–naphthyl and 2-naphthyl). In some embodiments, an aryl group has 14 ring 11760147.1 carbon atoms (“C14aryl”; e.g., anthracyl). “Aryl” also includes ring systems wherein the aryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the radical or point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system. Unless otherwise specified, each instance of an aryl group is independently unsubstituted (an “unsubstituted aryl”) or substituted (a “substituted aryl”) with one or more substituents. In certain embodiments, the aryl group is an unsubstituted C6-14aryl. In certain embodiments, the aryl group is a substituted C6-14 aryl. “Aralkyl” is a subset of “alkyl” and refers to an alkyl group substituted by an aryl group, wherein the point of attachment is on the alkyl moiety. The term “heteroaryl” refers to a radical of a 5-14 membered monocyclic or polycyclic (e.g., bicyclic, tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 ^ electrons shared in a cyclic array) having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-14 membered heteroaryl”). In heteroaryl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. Heteroaryl polycyclic ring systems can include one or more heteroatoms in one or both rings. “Heteroaryl” includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heteroaryl ring system. “Heteroaryl” also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused polycyclic (aryl / heteroaryl) ring system. Polycyclic heteroaryl groups wherein one ring does not contain a heteroatom (e.g., indolyl, quinolinyl, carbazolyl, and the like) the point of attachment can be on either ring, e.g., either the ring bearing a heteroatom (e.g., 2-indolyl) or the ring that does not contain a heteroatom (e.g., 5-indolyl). In certain embodiments, the heteroaryl is substituted or unsubstituted, 5- or 6-membered, monocyclic heteroaryl, wherein 1, 2, 3, or 4 atoms in the heteroaryl ring system are independently oxygen, nitrogen, or sulfur. In certain embodiments, the heteroaryl is substituted or unsubstituted, 9- or 10-membered, bicyclic heteroaryl, wherein 1, 2, 3, or 4 atoms in the heteroaryl ring system are independently oxygen, nitrogen, or sulfur. 11760147.1 In some embodiments, a heteroaryl group is a 5-10 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-10 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5-8 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-8 membered heteroaryl”). In some embodiments, a heteroaryl group is a 5-6 membered aromatic ring system having ring carbon atoms and 1–4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur (“5-6 membered heteroaryl”). In some embodiments, the 5-6 membered heteroaryl has 1–3 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl has 1–2 ring heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, the 5-6 membered heteroaryl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur. Unless otherwise specified, each instance of a heteroaryl group is independently unsubstituted (an “unsubstituted heteroaryl”) or substituted (a “substituted heteroaryl”) with one or more substituents. In certain embodiments, the heteroaryl group is an unsubstituted 5-14 membered heteroaryl. In certain embodiments, the heteroaryl group is a substituted 5-14 membered heteroaryl. Exemplary 5-membered heteroaryl groups containing 1 heteroatom include pyrrolyl, furanyl, and thiophenyl. Exemplary 5-membered heteroaryl groups containing 2 heteroatoms include imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl. Exemplary 5- membered heteroaryl groups containing 3 heteroatoms include triazolyl, oxadiazolyl, and thiadiazolyl. Exemplary 5-membered heteroaryl groups containing 4 heteroatoms include tetrazolyl. Exemplary 6-membered heteroaryl groups containing 1 heteroatom include pyridinyl. Exemplary 6-membered heteroaryl groups containing 2 heteroatoms include pyridazinyl, pyrimidinyl, and pyrazinyl. Exemplary 6-membered heteroaryl groups containing 3 or 4 heteroatoms include triazinyl and tetrazinyl, respectively. Exemplary 7-membered heteroaryl groups containing 1 heteroatom include azepinyl, oxepinyl, and thiepinyl. Exemplary 5,6- bicyclic heteroaryl groups include indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl. Exemplary 6,6-bicyclic heteroaryl groups include 11760147.1 naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. Exemplary tricyclic heteroaryl groups include phenanthridinyl, dibenzofuranyl, carbazolyl, acridinyl, phenothiazinyl, phenoxazinyl, and phenazinyl. “Heteroaralkyl” is a subset of “alkyl” and refers to an alkyl group substituted by a heteroaryl group, wherein the point of attachment is on the alkyl moiety. The term “unsaturated bond” refers to a double or triple bond. The term “unsaturated” or “partially unsaturated” refers to a moiety that includes at least one double or triple bond. The term “saturated” or “fully saturated” refers to a moiety that does not contain a double or triple bond, e.g., the moiety only contains single bonds. Affixing the suffix “-ene” to a group indicates the group is a divalent moiety, e.g., alkylene is the divalent moiety of alkyl, alkenylene is the divalent moiety of alkenyl, alkynylene is the divalent moiety of alkynyl, heteroalkylene is the divalent moiety of heteroalkyl, heteroalkenylene is the divalent moiety of heteroalkenyl, heteroalkynylene is the divalent moiety of heteroalkynyl, carbocyclylene is the divalent moiety of carbocyclyl, heterocyclylene is the divalent moiety of heterocyclyl, arylene is the divalent moiety of aryl, and heteroarylene is the divalent moiety of heteroaryl. A group is optionally substituted unless expressly provided otherwise. The term “optionally substituted” refers to being substituted or unsubstituted. In certain embodiments, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted. “Optionally substituted” refers to a group which is substituted or unsubstituted (e.g., “substituted” or “unsubstituted” alkyl, “substituted” or “unsubstituted” alkenyl, “substituted” or “unsubstituted” alkynyl, “substituted” or “unsubstituted” heteroalkyl, “substituted” or “unsubstituted” heteroalkenyl, “substituted” or “unsubstituted” heteroalkynyl, “substituted” or “unsubstituted” carbocyclyl, “substituted” or “unsubstituted” heterocyclyl, “substituted” or “unsubstituted” aryl or “substituted” or “unsubstituted” heteroaryl group). In general, the term “substituted” means that at least one hydrogen present on a group is replaced with a permissible substituent, e.g., a substituent which upon substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction. Unless otherwise indicated, a “substituted” group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the 11760147.1 substituent is either the same or different at each position. The term “substituted” is contemplated to include substitution with all permissible substituents of organic compounds, and includes any of the substituents described herein that results in the formation of a stable compound. The present disclosure contemplates any and all such combinations in order to arrive at a stable compound. For purposes of this disclosure, heteroatoms such as nitrogen may have hydrogen substituents and / or any suitable substituent as described herein which satisfy the valencies of the heteroatoms and results in the formation of a stable moiety. The disclosure is not limited in any manner by the exemplary substituents described herein. Exemplary carbon atom substituents include halogen, −CN, −NO2, −N3, −SO2H, −SO3H, −OH, −ORaa, −ON(Rbb)2, −N(Rbb)2, −N(Rbb)3+X−, −N(ORcc)Rbb, −SH, −SRaa, −SSRcc, −OP(=O)(N(Rbb)2)2, −NRbbP(=O)(Raa)2, −NRbbP(=O)(ORcc)2, −NRbbP(=O)(N(Rbb)2)2, −P(Rcc)2, −P(ORcc)2, −P(Rcc)3+X−, −P(ORcc)3+X−, −P(Rcc)4, −P(ORcc)4, −OP(Rcc)2, −OP(Rcc)3+X−, −OP(ORcc)2, −OP(ORcc)3+X−, −OP(Rcc)4, −OP(ORcc)4, −B(Raa)2, −B(ORcc)2, −BRaa(ORcc), C1–20alkyl, C1–20perhaloalkyl, C1–20alkenyl, C1–20alkynyl, heteroC1–20alkyl, heteroC1–20alkenyl, heteroC1–20 alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups; wherein X−is a counterion; or two geminal hydrogens on a carbon atom are replaced with the group =O, =S, =NN(Rbb)2, =NNRbbC(=O)Raa, =NNRbbC(=O)ORaa, =NNRbbS(=O)2Raa, =NRbb, or =NORcc; wherein: each instance of Raais, independently, selected from C1–20 alkyl, C1–20 perhaloalkyl, C1–20 alkenyl, C1–20alkynyl, heteroC1–20alkyl, heteroC1–20alkenyl, heteroC1–20alkynyl, C3-10carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two Raagroups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, 11760147.1 wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups; each instance of Rbbis, independently, selected from hydrogen, −OH, −ORaa, −N(Rcc)2, −CN, −C(=O)Raa, −C(=O)N(Rcc)2, −CO2Raa, −SO2Raa, −C(=NRcc)ORaa, −C(=NRcc)N(Rcc)2, −SO2N(Rcc)2, −SO2Rcc, −SO2ORcc, −SORaa, −C(=S)N(Rcc)2, −C(=O)SRcc, −C(=S)SRcc, −P(=O)(Raa)2, −P(=O)(ORcc)2, −P(=O)(N(Rcc)2)2, C1–20alkyl, C1–20perhaloalkyl, C1–20alkenyl, C1–20 alkynyl, heteroC1–20alkyl, heteroC1–20alkenyl, heteroC1–20alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two Rbbgroups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups; each instance of Rccis, independently, selected from hydrogen, C1–20alkyl, C1–20perhaloalkyl, C1–20alkenyl, C1–20alkynyl, heteroC1–20alkyl, heteroC1–20alkenyl, heteroC1–20alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two Rccgroups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups; each instance of Rddis, independently, selected from halogen, −CN, −NO2, −N3, −SO2H, −SO3H, −OH, −ORee, −ON(Rff)2, −N(Rff)2, −N(Rff)3+X−, −N(ORee)Rff, −SH, −SRee, −SSRee, −NRffC(=O)Ree, −NRffCO2Ree, −NRffC(=O)N(Rff)2, −C(=NRff)ORee, −OC(=NRff)Ree, −OC(=NRff)ORee, −C(=NRff)N(Rff)2, −OC(=NRff)N(Rff)2, −NRffC(=NRff)N(Rff)2, −NRffSO2Ree, −SO2N(Rff)2, −SO2Ree, −SO2ORee, −OSO2Ree, −S(=O)Ree, −Si(Ree)3, −OSi(Ree)3, −C(=S)N(Rff)2, −C(=O)SRee, −C(=S)SRee, −SC(=S)SRee, −P(=O)(ORee)2, −P(=O)(Ree)2, −OP(=O)(Ree)2, −OP(=O)(ORee)2, C1–10alkyl, C1–10perhaloalkyl, C1–10alkenyl, C1–10alkynyl, heteroC1–10alkyl, heteroC1–10alkenyl, heteroC1–10alkynyl, C3-10 carbocyclyl, 3-10 membered heterocyclyl, C6-10 aryl, and 5-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rgggroups, or two geminal Rddsubstituents are joined to form =O or =S; wherein X−is a counterion; 11760147.1 each instance of Reeis, independently, selected from C1–10alkyl, C1–10perhaloalkyl, C1–10alkenyl, C1–10 alkynyl, heteroC1–10 alkyl, heteroC1–10 alkenyl, heteroC1–10 alkynyl, C3-10 carbocyclyl, C6-10aryl, 3-10 membered heterocyclyl, and 3-10 membered heteroaryl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rgggroups; each instance of Rffis, independently, selected from hydrogen, C1–10 alkyl, C1–10 perhaloalkyl, C1–10alkenyl, C1–10alkynyl, heteroC1–10alkyl, heteroC1–10alkenyl, heteroC1–10alkynyl, C3-10 carbocyclyl, 3-10 membered heterocyclyl, C6-10 aryl, and 5-10 membered heteroaryl, or two Rffgroups are joined to form a 3-10 membered heterocyclyl or 5-10 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rgggroups; each instance of Rggis, independently, halogen, −CN, −NO2, −N3, −SO2H, −SO3H, −OH, −OC1–6alkyl, −ON(C1–6alkyl)2, −N(C1–6alkyl)2, −N(C1–6alkyl)3+X−, −NH(C1–6alkyl)2+X−, −NH2(C1–6 alkyl)+X−, −NH3+X−, −N(OC1–6 alkyl)(C1–6 alkyl), −N(OH)(C1–6 alkyl), −NH(OH), −SH, −SC1–6 alkyl, −SS(C1–6 alkyl), −C(=O)(C1–6 alkyl), −CO2H, −CO2(C1–6 alkyl), −OC(=O)(C1–6alkyl), −OCO2(C1–6alkyl), −C(=O)NH2, −C(=O)N(C1–6alkyl)2, −OC(=O)NH(C1–6 alkyl), −NHC(=O)( C1–6 alkyl), −N(C1–6 alkyl)C(=O)( C1–6 alkyl), −NHCO2(C1–6 alkyl), −NHC(=O)N(C1–6 alkyl)2, −NHC(=O)NH(C1–6 alkyl), −NHC(=O)NH2, −C(=NH)O(C1–6alkyl), −OC(=NH)(C1–6alkyl), −OC(=NH)OC1–6alkyl, −C(=NH)N(C1–6alkyl)2, −C(=NH)NH(C1–6alkyl), −C(=NH)NH2, −OC(=NH)N(C1–6alkyl)2, −OC(NH)NH(C1–6alkyl), −OC(NH)NH2, −NHC(NH)N(C1–6 alkyl)2, −NHC(=NH)NH2, −NHSO2(C1–6 alkyl), −SO2N(C1–6alkyl)2, −SO2NH(C1–6alkyl), −SO2NH2, −SO2C1–6alkyl, −SO2OC1–6alkyl, −OSO2C1–6alkyl, −SOC1–6alkyl, −Si(C1–6alkyl)3, −OSi(C1–6alkyl)3−C(=S)N(C1–6alkyl)2, C(=S)NH(C1–6 alkyl), C(=S)NH2, −C(=O)S(C1–6 alkyl), −C(=S)SC1–6 alkyl, −SC(=S)SC1–6 alkyl, −P(=O)(OC1–6 alkyl)2, −P(=O)(C1–6 alkyl)2, −OP(=O)(C1–6 alkyl)2, −OP(=O)(OC1–6 alkyl)2, C1–10alkyl, C1–10perhaloalkyl, C1–10alkenyl, C1–10alkynyl, heteroC1–10alkyl, heteroC1–10alkenyl, heteroC1–10 alkynyl, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered heterocyclyl, or 5-10 membered heteroaryl; or two geminal Rggsubstituents can be joined to form =O or =S; and each X−is a counterion. In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl, −ORaa, 11760147.1 −OCO2Raa, −OC(=O)N(Rbb)2, −NRbbC(=O)Raa, −NRbbCO2Raa, or −NRbbC(=O)N(Rbb)2. In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1–10alkyl, −ORaa, −SRaa, −N(Rbb)2, −OC(=O)N(Rbb)2, −NRbbC(=O)Raa, −NRbbCO2Raa, or −NRbbC(=O)N(Rbb)2, wherein Raais hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1–10alkyl, an oxygen protecting group (e.g., silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl) when attached to an oxygen atom, or a sulfur protecting group (e.g., acetamidomethyl, t-Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl) when attached to a sulfur atom; and each Rbbis independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1–10 alkyl, or a nitrogen protecting group (e.g., Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts). In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl, −ORaa, −SRaa, −N(Rbb)2, –CN, –SCN, or –NO2. In certain embodiments, each carbon atom substituent is independently halogen, substituted (e.g., substituted with one or more halogen moieties) or unsubstituted C1–10alkyl, −ORaa, −SRaa, −N(Rbb)2, –CN, –SCN, or –NO2, wherein Raais hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1–10 alkyl, an oxygen protecting group (e.g., silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl) when attached to an oxygen atom, or a sulfur protecting group (e.g., acetamidomethyl, t-Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl) when attached to a sulfur atom; and each Rbbis independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1–10alkyl, or a nitrogen protecting group (e.g., Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts). In certain embodiments, the molecular weight of a carbon atom substituent is lower than 250, lower than 200, lower than 150, lower than 100, or lower than 50 g / mol. In certain embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, nitrogen, and / or silicon atoms. In certain embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, and / or nitrogen atoms. In certain embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, and / or iodine atoms. In certain 11760147.1 embodiments, a carbon atom substituent consists of carbon, hydrogen, fluorine, and / or chlorine atoms. The term “halo” or “halogen” refers to fluorine (fluoro, −F), chlorine (chloro, −Cl), bromine (bromo, −Br), or iodine (iodo, −I). The term “hydroxyl” or “hydroxy” refers to the group −OH. The term “substituted hydroxyl” or “substituted hydroxyl,” by extension, refers to a hydroxyl group wherein the oxygen atom directly attached to the parent molecule is substituted with a group other than hydrogen, and includes groups selected from −ORaa, −ON(Rbb)2, −OC(=O)SRaa, −OC(=O)Raa, −OCO2Raa, −OC(=O)N(Rbb)2, −OC(=NRbb)Raa, −OC(=NRbb)ORaa, −OC(=NRbb)N(Rbb)2, −OS(=O)Raa, −OSO2Raa, −OSi(Raa)3, −OP(Rcc)2, −OP(Rcc)3+X−, −OP(ORcc)2, −OP(ORcc)3+X−, −OP(=O)(Raa)2, −OP(=O)(ORcc)2, and −OP(=O)(N(Rbb))2, wherein X−, Raa, Rbb, and Rccare as defined herein. The term “thiol” or “thio” refers to the group –SH. The term “substituted thiol” or “substituted thio,” by extension, refers to a thiol group wherein the sulfur atom directly attached to the parent molecule is substituted with a group other than hydrogen, and includes groups selected from –SRaa, –S=SRcc, –SC(=S)SRaa, –SC(=S)ORaa, –SC(=S) N(Rbb)2, –SC(=O)SRaa, –SC(=O)ORaa, –SC(=O)N(Rbb)2, and –SC(=O)Raa, wherein Raaand Rccare as defined herein. The term “amino” refers to the group −NH2. The term “substituted amino,” by extension, refers to a monosubstituted amino, a disubstituted amino, or a trisubstituted amino. In certain embodiments, the “substituted amino” is a monosubstituted amino or a disubstituted amino group. The term “monosubstituted amino” refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with one hydrogen and one group other than hydrogen, and includes groups selected from −NH(Rbb), −NHC(=O)Raa, −NHCO2Raa, −NHC(=O)N(Rbb)2, −NHC(=NRbb)N(Rbb)2, −NHSO2Raa, −NHP(=O)(ORcc)2, and −NHP(=O)(N(Rbb)2)2, wherein Raa, Rbband Rccare as defined herein, and wherein Rbbof the group −NH(Rbb) is not hydrogen. The term “disubstituted amino” refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with two groups other than hydrogen, and includes groups selected from −N(Rbb)2, −NRbbC(=O)Raa, −NRbbCO2Raa, −NRbbC(=O)N(Rbb)2, −NRbbC(=NRbb)N(Rbb)2, −NRbbSO2Raa, −NRbbP(=O)(ORcc)2, and −NRbbP(=O)(N(Rbb)2)2, 11760147.1 wherein Raa, Rbb, and Rccare as defined herein, with the proviso that the nitrogen atom directly attached to the parent molecule is not substituted with hydrogen. The term “trisubstituted amino” refers to an amino group wherein the nitrogen atom directly attached to the parent molecule is substituted with three groups, and includes groups selected from −N(Rbb)3 and −N(Rbb)3+X−, wherein Rbband X−are as defined herein. The term “acyl” refers to a group having the general formula −C(=O)RX1, −C(=O)ORX1, −C(=O)−O−C(=O)RX1, −C(=O)SRX1, −C(=O)N(RX1)2, −C(=S)RX1, −C(=S)N(RX1)2, and −C(=S)S(RX1), −C(=NRX1)RX1, −C(=NRX1)ORX1, −C(=NRX1)SRX1, and −C(=NRX1)N(RX1)2, wherein RX1is hydrogen; halogen; substituted or unsubstituted hydroxyl; substituted or unsubstituted thiol; substituted or unsubstituted amino; substituted or unsubstituted acyl, cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkyl; cyclic or acyclic, substituted or unsubstituted, branched or unbranched alkenyl; substituted or unsubstituted alkynyl; substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, mono- or di- aliphaticamino, mono- or di- heteroaliphaticamino, mono- or di- alkylamino, mono- or di- heteroalkylamino, mono- or di-arylamino, or mono- or di-heteroarylamino; or two RX1groups taken together form a 5- to 6-membered heterocyclic ring. Exemplary acyl groups include aldehydes (−CHO), carboxylic acids (−CO2H), ketones, acyl halides, esters, amides, imines, carbonates, carbamates, and ureas. Acyl substituents include, but are not limited to, any of the substituents described herein, that result in the formation of a stable moiety (e.g., aliphatic, alkyl, alkenyl, alkynyl, heteroaliphatic, heterocyclic, aryl, heteroaryl, acyl, oxo, imino, thiooxo, cyano, isocyano, amino, azido, nitro, hydroxyl, thiol, halo, aliphaticamino, heteroaliphaticamino, alkylamino, heteroalkylamino, arylamino, heteroarylamino, alkylaryl, arylalkyl, aliphaticoxy, heteroaliphaticoxy, alkyloxy, heteroalkyloxy, aryloxy, heteroaryloxy, aliphaticthioxy, heteroaliphaticthioxy, alkylthioxy, heteroalkylthioxy, arylthioxy, heteroarylthioxy, acyloxy, and the like, each of which may or may not be further substituted). The term “carbonyl” refers to a group wherein the carbon directly attached to the parent molecule is sp2hybridized, and is substituted with an oxygen, nitrogen or sulfur atom, e.g., a group selected from ketones (–C(=O)Raa), carboxylic acids (–CO2H), aldehydes (–CHO), esters 11760147.1 (–CO2Raa, –C(=O)SRaa, –C(=S)SRaa), amides (–C(=O)N(Rbb)2, –C(=O)NRbbSO2Raa, −C(=S)N(Rbb)2), and imines (–C(=NRbb)Raa, –C(=NRbb)ORaa), –C(=NRbb)N(Rbb)2), wherein Raaand Rbbare as defined herein. The term “silyl” refers to the group –Si(Raa)3, wherein Raais as defined herein. The term “oxo” refers to the group =O, and the term “thiooxo” refers to the group =S. Nitrogen atoms can be substituted or unsubstituted as valency permits, and include primary, secondary, tertiary, and quaternary nitrogen atoms. Exemplary nitrogen atom substituents include hydrogen, −OH, −ORaa, −N(Rcc)2, −CN, −C(=O)Raa, −C(=O)N(Rcc)2, −SO2ORcc, −SORaa, −C(=S)N(Rcc)2, −C(=O)SRcc, −C(=S)SRcc, −P(=O)(ORcc)2, −P(=O)(Raa)2, −P(=O)(N(Rcc)2)2, C1–20alkyl, C1–20perhaloalkyl, C1–20alkenyl, C1–20alkynyl, hetero C1–20alkyl, hetero C1–20 alkenyl, hetero C1–20 alkynyl, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two Rccgroups attached to an N atom are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups, and wherein Raa, Rbb, Rccand Rddare as defined above. In certain embodiments, each nitrogen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl, −C(=O)Raa, −CO2Raa, −C(=O)N(Rbb)2, or a nitrogen protecting group. In certain embodiments, each nitrogen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, −C(=O)Raa, −CO2Raa, −C(=O)N(Rbb)2, or a nitrogen protecting group, wherein Raais hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10alkyl, or an oxygen protecting group when attached to an oxygen atom; and each Rbbis independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, or a nitrogen protecting group. In certain embodiments, each nitrogen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl or a nitrogen protecting group. In certain embodiments, the substituent present on the nitrogen atom is a nitrogen protecting group (also referred to herein as an “amino protecting group”). Nitrogen protecting groups include −OH, −ORaa, −N(Rcc)2, −C(=O)Raa, −C(=O)N(Rcc)2, −CO2Raa, −SO2Raa, 11760147.1 −C(=NRcc)Raa, −C(=NRcc)ORaa, −C(=NRcc)N(Rcc)2, −SO2N(Rcc)2, −SO2Rcc, −SO2ORcc, −SORaa, −C(=S)N(Rcc)2, −C(=O)SRcc, −C(=S)SRcc, C1–10 alkyl (e.g., aralkyl, heteroaralkyl), C1–20 alkenyl, C1–20alkynyl, hetero C1–20alkyl, hetero C1–20alkenyl, hetero C1–20alkynyl, C3-10carbocyclyl, 3-14 membered heterocyclyl, C6-14aryl, and 5-14 membered heteroaryl groups, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, carbocyclyl, heterocyclyl, aralkyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 Rddgroups, and wherein Raa, Rbb, Rccand Rddare as defined herein. Nitrogen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3rdedition, John Wiley & Sons, 1999, incorporated herein by reference. For example, in certain embodiments, at least one nitrogen protecting group is an amide group (e.g., a moiety that include the nitrogen atom to which the nitrogen protecting groups (e.g., −C(=O)Raa) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3-phenylpropanamide, picolinamide, 3-pyridylcarboxamide, N-benzoylphenylalanyl derivatives, benzamide, p-phenylbenzamide, o- nitophenylacetamide, o-nitrophenoxyacetamide, acetoacetamide, (N’- dithiobenzyloxyacylamino)acetamide, 3-(p-hydroxyphenyl)propanamide, 3-(o- nitrophenyl)propanamide, 2-methyl-2-(o-nitrophenoxy)propanamide, 2-methyl-2-(o- phenylazophenoxy)propanamide, 4-chlorobutanamide, 3-methyl-3-nitrobutanamide, o- nitrocinnamide, N-acetylmethionine derivatives, o-nitrobenzamide, and o- (benzoyloxymethyl)benzamide. In certain embodiments, at least one nitrogen protecting group is a carbamate group (e.g., a moiety that include the nitrogen atom to which the nitrogen protecting groups (e.g., −C(=O)ORaa) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of methyl carbamate, ethyl carbamate, 9- fluorenylmethyl carbamate (Fmoc), 9-(2-sulfo)fluorenylmethyl carbamate, 9-(2,7- dibromo)fluoroenylmethyl carbamate, 2,7-di-t-butyl-[9-(10,10-dioxo-10,10,10,10- tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4-methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2- 11760147.1 phenylethyl carbamate (hZ), 1–(1-adamantyl)-1-methylethyl carbamate (Adpoc), 1,1-dimethyl- 2-haloethyl carbamate, 1,1-dimethyl-2,2-dibromoethyl carbamate (DB-t-BOC), 1,1-dimethyl- 2,2,2-trichloroethyl carbamate (TCBOC), 1-methyl-1-(4-biphenylyl)ethyl carbamate (Bpoc), 1- (3,5-di-t-butylphenyl)-1-methylethyl carbamate (t-Bumeoc), 2-(2′- and 4′-pyridyl)ethyl carbamate (Pyoc), 2-(N,N-dicyclohexylcarboxamido)ethyl carbamate, t-butyl carbamate (BOC or Boc), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1- isopropylallyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4-nitrocinnamyl carbamate (Noc), 8-quinolyl carbamate, N-hydroxypiperidinyl carbamate, alkyldithio carbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p-nitobenzyl carbamate, p-bromobenzyl carbamate, p-chlorobenzyl carbamate, 2,4-dichlorobenzyl carbamate, 4-methylsulfinylbenzyl carbamate (Msz), 9-anthrylmethyl carbamate, diphenylmethyl carbamate, 2-methylthioethyl carbamate, 2-methylsulfonylethyl carbamate, 2-(p-toluenesulfonyl)ethyl carbamate, [2-(1,3- dithianyl)]methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc), 2,4- dimethylthiophenyl carbamate (Bmpc), 2-phosphonioethyl carbamate (Peoc), 2- triphenylphosphonioisopropyl carbamate (Ppoc), 1,1-dimethyl-2-cyanoethyl carbamate, m- chloro-p-acyloxybenzyl carbamate, p-(dihydroxyboryl)benzyl carbamate, 5- benzisoxazolylmethyl carbamate, 2-(trifluoromethyl)-6-chromonylmethyl carbamate (Tcroc), m- nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4- dimethoxy-6-nitrobenzyl carbamate, phenyl(o-nitrophenyl)methyl carbamate, t-amyl carbamate, S-benzyl thiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p-decyloxybenzyl carbamate, 2,2- dimethoxyacylvinyl carbamate, o-(N,N-dimethylcarboxamido)benzyl carbamate, 1,1-dimethyl- 3-(N,N-dimethylcarboxamido)propyl carbamate, 1,1-dimethylpropynyl carbamate, di(2- pyridyl)methyl carbamate, 2-furanylmethyl carbamate, 2-iodoethyl carbamate, isoborynl carbamate, isobutyl carbamate, isonicotinyl carbamate, p-(p’-methoxyphenylazo)benzyl carbamate, 1-methylcyclobutyl carbamate, 1-methylcyclohexyl carbamate, 1-methyl-1- cyclopropylmethyl carbamate, 1-methyl-1-(3,5-dimethoxyphenyl)ethyl carbamate, 1-methyl-1- (p-phenylazophenyl)ethyl carbamate, 1-methyl-1-phenylethyl carbamate, 1-methyl-1-(4- pyridyl)ethyl carbamate, phenyl carbamate, p-(phenylazo)benzyl carbamate, 2,4,6-tri-t- butylphenyl carbamate, 4-(trimethylammonium)benzyl carbamate, and 2,4,6-trimethylbenzyl carbamate. 11760147.1 In certain embodiments, at least one nitrogen protecting group is a sulfonamide group (e.g., a moiety that include the nitrogen atom to which the nitrogen protecting groups (e.g., −S(=O)2Raa) is directly attached). In certain such embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6-trimethyl-4-methoxybenzenesulfonamide (Mtr), 2,4,6- trimethoxybenzenesulfonamide (Mtb), 2,6-dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl-4-methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6-trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β- trimethylsilylethanesulfonamide (SES), 9-anthracenesulfonamide, 4-(4′,8′- dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, and phenacylsulfonamide. In certain embodiments, each nitrogen protecting group, together with the nitrogen atom to which the nitrogen protecting group is attached, is independently selected from the group consisting of phenothiazinyl-(10)-acyl derivatives, N’-p-toluenesulfonylaminoacyl derivatives, N’-phenylaminothioacyl derivatives, N-benzoylphenylalanyl derivatives, N-acetylmethionine derivatives, 4,5-diphenyl-3-oxazolin-2-one, N-phthalimide, N-dithiasuccinimide (Dts), N-2,3- diphenylmaleimide, N-2,5-dimethylpyrrole, N-1,1,4,4-tetramethyldisilylazacyclopentane adduct (STABASE), 5-substituted 1,3-dimethyl-1,3,5-triazacyclohexan-2-one, 5-substituted 1,3- dibenzyl-1,3,5-triazacyclohexan-2-one, 1-substituted 3,5-dinitro-4-pyridone, N-methylamine, N- allylamine, N-[2-(trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1- isopropyl-4-nitro-2-oxo-3-pyroolin-3-yl)amine, quaternary ammonium salts, N-benzylamine, N- di(4-methoxyphenyl)methylamine, N-5-dibenzosuberylamine, N-triphenylmethylamine (Tr), N- [(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluorenylamine (PhF), N-2,7- dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2-picolylamino N’- oxide, N-1,1-dimethylthiomethyleneamine, N-benzylideneamine, N-p- methoxybenzylideneamine, N-diphenylmethyleneamine, N-[(2-pyridyl)mesityl]methyleneamine, N-(N’,N’-dimethylaminomethylene)amine, N-p-nitrobenzylideneamine, N-salicylideneamine, N- 5-chlorosalicylideneamine, N-(5-chloro-2-hydroxyphenyl)phenylmethyleneamine, N- cyclohexylideneamine, N-(5,5-dimethyl-3-oxo-1-cyclohexenyl)amine, N-borane derivatives, N- diphenylborinic acid derivatives, N-[phenyl(pentaacylchromium- or tungsten)acyl]amine, N- 11760147.1 copper chelate, N-zinc chelate, N-nitroamine, N-nitrosoamine, amine N-oxide, diphenylphosphinamide (Dpp), dimethylthiophosphinamide (Mpt), diphenylthiophosphinamide (Ppt), dialkyl phosphoramidates, dibenzyl phosphoramidate, diphenyl phosphoramidate, benzenesulfenamide, o-nitrobenzenesulfenamide (Nps), 2,4-dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4-methoxybenzenesulfenamide, triphenylmethylsulfenamide, and 3-nitropyridinesulfenamide (Npys). In some embodiments, two instances of a nitrogen protecting group together with the nitrogen atoms to which the nitrogen protecting groups are attached are N,N’-isopropylidenediamine. In certain embodiments, at least one nitrogen protecting group is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts. In certain embodiments, each oxygen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, −C(=O)Raa, −CO2Raa, −C(=O)N(Rbb)2, or an oxygen protecting group. In certain embodiments, each oxygen atom substituents is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl, −C(=O)Raa, −CO2Raa, −C(=O)N(Rbb)2, or an oxygen protecting group, wherein Raais hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10alkyl, or an oxygen protecting group when attached to an oxygen atom; and each Rbbis independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, or a nitrogen protecting group. In certain embodiments, each oxygen atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6alkyl or an oxygen protecting group. In certain embodiments, the substituent present on an oxygen atom is an oxygen protecting group (also referred to herein as an “hydroxyl protecting group”). Oxygen protecting wherein X−, Raa, Rbb, and Rccare as defined herein. Oxygen protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3rdedition, John Wiley & Sons, 1999, incorporated herein by reference. In certain embodiments, each oxygen protecting group, together with the oxygen atom to which the oxygen protecting group is attached, is selected from the group consisting of methyl, 11760147.1 methoxymethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p- methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2-methoxyethoxymethyl (MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2- (trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3-bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, 4-methoxytetrahydropyranyl (MTHP), 4- methoxytetrahydrothiopyranyl, 4-methoxytetrahydrothiopyranyl S,S-dioxide, 1-[(2-chloro-4- methyl)phenyl]-4-methoxypiperidin-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-yl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1-benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2- (phenylselenyl)ethyl, t-butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl (Bn), p-methoxybenzyl (PMB), 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p- halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl, p-phenylbenzyl, 2-picolyl, 4-picolyl, 3-methyl- 2-picolyl N-oxido, diphenylmethyl, p,p’-dinitrobenzhydryl, 5-dibenzosuberyl, triphenylmethyl, α-naphthyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di(p- methoxyphenyl)phenylmethyl, tri(p-methoxyphenyl)methyl, 4-(4’- bromophenacyloxyphenyl)diphenylmethyl, 4,4′,4″-tris(4,5-dichlorophthalimidophenyl)methyl, 4,4′,4″-tris(levulinoyloxyphenyl)methyl, 4,4′,4″-tris(benzoyloxyphenyl)methyl, 4,4’-Dimethoxy- 3"‘-[N-(imidazolylmethyl) ]trityl Ether (IDTr-OR), 4,4’-Dimethoxy-3"‘-[N- (imidazolylethyl)carbamoyl]trityl Ether (IETr-OR), 1,1-bis(4-methoxyphenyl)-1′-pyrenylmethyl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9-phenyl-10-oxo)anthryl, 1,3-benzodithiolan-2-yl, benzisothiazolyl S,S-dioxido, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethylthexylsilyl, t- butyldimethylsilyl (TBDMS), t-butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl, diphenylmethylsilyl (DPMS), t-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3- phenylpropionate, 4-oxopentanoate (levulinate), 4,4-(ethylenedithio)pentanoate (levulinoyldithioacetal), pivaloate, adamantoate, crotonate, 4-methoxycrotonate, benzoate, p- phenylbenzoate, 2,4,6-trimethylbenzoate (mesitoate), methyl carbonate, 9-fluorenylmethyl 11760147.1 carbonate (Fmoc), ethyl carbonate, 2,2,2-trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(phenylsulfonyl) ethyl carbonate (Psec), 2-(triphenylphosphonio) ethyl carbonate (Peoc), isobutyl carbonate, vinyl carbonate, allyl carbonate, t-butyl carbonate (BOC or Boc), p-nitrophenyl carbonate, benzyl carbonate, p-methoxybenzyl carbonate, 3,4- dimethoxybenzyl carbonate, o-nitrobenzyl carbonate, p-nitrobenzyl carbonate, S-benzyl thiocarbonate, 4-ethoxy-1-napththyl carbonate, methyl dithiocarbonate, 2-iodobenzoate, 4- azidobutyrate, 4-nitro-4-methylpentanoate, o-(dibromomethyl)benzoate, 2- formylbenzenesulfonate, 2-(methylthiomethoxy)ethyl carbonate (MTMEC-OR), 4- (methylthiomethoxy)butyrate, 2-(methylthiomethoxymethyl)benzoate, 2,6-dichloro-4- methylphenoxyacetate, 2,6-dichloro-4-(1,1,3,3-tetramethylbutyl)phenoxyacetate, 2,4-bis(1,1- dimethylpropyl)phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoate, (E)-2- methyl-2-butenoate, o-(methoxyacyl)benzoate, α-naphthoate, nitrate, alkyl N,N,N’,N’- tetramethylphosphorodiamidate, alkyl N-phenylcarbamate, borate, dimethylphosphinothioyl, alkyl 2,4-dinitrophenylsulfenate, sulfate, methanesulfonate (mesylate), benzylsulfonate, and tosylate (Ts). In certain embodiments, at least one oxygen protecting group is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, t-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl. In certain embodiments, each sulfur atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, −C(=O)Raa, −CO2Raa, −C(=O)N(Rbb)2, or a sulfur protecting group. In certain embodiments, each sulfur atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, −C(=O)Raa, −CO2Raa, −C(=O)N(Rbb)2, or a sulfur protecting group, wherein Raais hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10alkyl, or an oxygen protecting group when attached to an oxygen atom; and each Rbbis independently hydrogen, substituted (e.g., substituted with one or more halogen) or unsubstituted C1-10 alkyl, or a nitrogen protecting group. In certain embodiments, each sulfur atom substituent is independently substituted (e.g., substituted with one or more halogen) or unsubstituted C1-6 alkyl or a sulfur protecting group. In certain embodiments, the substituent present on a sulfur atom is a sulfur protecting group (also referred to as a “thiol protecting group”). In some embodiments, each sulfur protecting group is selected from the group consisting of −Raa, −N(Rbb)2, −C(=O)SRaa, 11760147.1 −S(=O)Raa, −SO2Raa, −Si(Raa)3, −P(Rcc)2, −P(Rcc)3+X−, −P(ORcc)2, −P(ORcc)3+X−, −P(=O)(Raa)2, −P(=O)(ORcc)2, and −P(=O)(N(Rbb) 2)2, wherein Raa, Rbb, and Rccare as defined herein. Sulfur protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3rdedition, John Wiley & Sons, 1999, incorporated herein by reference. In certain embodiments, the molecular weight of a substituent is lower than 250, lower than 200, lower than 150, lower than 100, or lower than 50 g / mol. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, nitrogen, and / or silicon atoms. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, iodine, oxygen, sulfur, and / or nitrogen atoms. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, chlorine, bromine, and / or iodine atoms. In certain embodiments, a substituent consists of carbon, hydrogen, fluorine, and / or chlorine atoms. In certain embodiments, a substituent comprises 0, 1, 2, or 3 hydrogen bond donors. In certain embodiments, a substituent comprises 0, 1, 2, or 3 hydrogen bond acceptors. A “counterion” or “anionic counterion” is a negatively charged group associated with a positively charged group in order to maintain electronic neutrality. An anionic counterion may be monovalent (e.g., including one formal negative charge). An anionic counterion may also be multivalent (e.g., including more than one formal negative charge), such as divalent or trivalent. Exemplary counterions include halide ions (e.g., F–, Cl–, Br–, I–), NO3–, ClO4–, OH–, H2PO4–, HCO3−,HSO4–, sulfonate ions (e.g., methansulfonate, trifluoromethanesulfonate, p– toluenesulfonate, benzenesulfonate, 10–camphor sulfonate, naphthalene–2–sulfonate, naphthalene–1–sulfonic acid–5–sulfonate, ethan–1–sulfonic acid–2–sulfonate, and the like), carboxylate ions (e.g., acetate, propanoate, benzoate, glycerate, lactate, tartrate, glycolate, gluconate, and the like), BF4−, PF4–, PF6–, AsF6–, SbF6–, B[3,5-(CF3)2C6H3]4]–, B(C6F5)4−, BPh4–, Al(OC(CF3)3)4–, and carborane anions (e.g., CB11H12–or (HCB11Me5Br6)–). Exemplary counterions which may be multivalent include CO32−, HPO42−, PO43−,B4O72−, SO42−, S2O32−, carboxylate anions (e.g., tartrate, citrate, fumarate, maleate, malate, malonate, gluconate, succinate, glutarate, adipate, pimelate, suberate, azelate, sebacate, salicylate, phthalates, aspartate, glutamate, and the like), and carboranes. 11760147.1 Use of the phrase “at least one instance” refers to 1, 2, 3, 4, or more instances, but also encompasses a range, e.g., for example, from 1 to 4, from 1 to 3, from 1 to 2, from 2 to 4, from 2 to 3, or from 3 to 4 instances, inclusive. A “non-hydrogen group” refers to any group that is defined for a particular variable that is not hydrogen. The term “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this disclosure include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid or with organic acids, such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium, and N+(C1-4alkyl)4salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate. 11760147.1 The term “solvate” refers to forms of the compound, or a salt thereof, that are associated with a solvent, usually by a solvolysis reaction. This physical association may include hydrogen bonding. Conventional solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, and the like. The compounds described herein may be prepared, e.g., in crystalline form, and may be solvated. Suitable solvates include pharmaceutically acceptable solvates and further include both stoichiometric solvates and non-stoichiometric solvates. In certain instances, the solvate will be capable of isolation, for example, when one or more solvent molecules are incorporated in the crystal lattice of a crystalline solid. “Solvate” encompasses both solution-phase and isolatable solvates. Representative solvates include hydrates, ethanolates, and methanolates. The term “hydrate” refers to a compound that is associated with water. Typically, the number of the water molecules contained in a hydrate of a compound is in a definite ratio to the number of the compound molecules in the hydrate. Therefore, a hydrate of a compound may be represented, for example, by the general formula R⋅x H2O, wherein R is the compound, and x is a number greater than 0. A given compound may form more than one type of hydrate, including, e.g., monohydrates (x is 1), lower hydrates (x is a number greater than 0 and smaller than 1, e.g., hemihydrates (R⋅0.5 H2O)), and polyhydrates (x is a number greater than 1, e.g., dihydrates (R⋅2 H2O) and hexahydrates (R⋅6 H2O)). The term “tautomers” or “tautomeric” refers to two or more interconvertible compounds resulting from at least one formal migration of a hydrogen atom and at least one change in valency (e.g., a single bond to a double bond, a triple bond to a single bond, or vice versa). The exact ratio of the tautomers depends on several factors, including temperature, solvent, and pH. Tautomerizations (i.e., the reaction providing a tautomeric pair) may catalyzed by acid or base. Exemplary tautomerizations include keto-to-enol, amide-to-imide, lactam-to-lactim, enamine-to- imine, and enamine-to-(a different enamine) tautomerizations. It is also to be understood that compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”. Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric center, for example, it is bonded to four different groups, a pair 11760147.1 of enantiomers is possible. An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (−)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”. The term “crystalline” or “crystalline form” refers to a solid form substantially exhibiting three-dimensional order. In certain embodiments, a crystalline form of a solid is a solid form that is substantially not amorphous. In certain embodiments, the X-ray powder diffraction (XRPD) pattern of a crystalline form includes one or more sharply defined peaks. The term “co-crystal” refers to a crystalline structure comprising at least two different components (e.g., a compound disclosed herein and an acid), wherein each of the components is independently an atom, ion, or molecule. In certain embodiments, none of the components is a solvent. In certain embodiments, at least one of the components is a solvent. A co-crystal of a compound disclosed herein and an acid is different from a salt formed from a compound disclosed herein and the acid. In the salt, a compound disclosed herein is complexed with the acid in a way that proton transfer (e.g., a complete proton transfer) from the acid to a compound disclosed herein easily occurs at room temperature. In the co-crystal, however, a compound disclosed herein is complexed with the acid in a way that proton transfer from the acid to a compound disclosed herein does not easily occur at room temperature. In certain embodiments, in the co-crystal, there is no proton transfer from the acid to a compound disclosed herein. In certain embodiments, in the co-crystal, there is partial proton transfer from the acid to a compound disclosed herein. Co-crystals may be useful to improve the properties (e.g., solubility, stability, and ease of formulation) of a compound disclosed herein. The term “polymorph” refers to a crystalline form of a compound (or a salt, hydrate, or solvate thereof). All polymorphs have the same elemental composition. Different crystalline forms usually have different X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability, and solubility. Recrystallization solvent, rate of crystallization, storage temperature, and other factors may cause one crystal form to dominate. Various polymorphs of a compound can be prepared by crystallization under different conditions. 11760147.1 The term “small molecule” refers to molecules, whether naturally occurring or artificially created (e.g., via chemical synthesis) that have a relatively low molecular weight. Typically, a small molecule is an organic compound (e.g., it contains carbon). The small molecule may contain multiple carbon-carbon bonds, stereocenters, and other functional groups (e.g., amines, hydroxyl, carbonyls, and heterocyclic rings, etc.). In certain embodiments, the molecular weight of a small molecule is not more than about 1,000 g / mol, not more than about 900 g / mol, not more than about 800 g / mol, not more than about 700 g / mol, not more than about 600 g / mol, not more than about 500 g / mol, not more than about 400 g / mol, not more than about 300 g / mol, not more than about 200 g / mol, or not more than about 100 g / mol. In certain embodiments, the molecular weight of a small molecule is at least about 100 g / mol, at least about 200 g / mol, at least about 300 g / mol, at least about 400 g / mol, at least about 500 g / mol, at least about 600 g / mol, at least about 700 g / mol, at least about 800 g / mol, or at least about 900 g / mol, or at least about 1,000 g / mol. Combinations of the above ranges (e.g., at least about 200 g / mol and not more than about 500 g / mol) are also possible. In certain embodiments, the small molecule is a therapeutically active agent such as a drug (e.g., a molecule approved by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (C.F.R.)). The small molecule may also be complexed with one or more metal atoms and / or metal ions. In this instance, the small molecule is also referred to as a “small organometallic molecule.” Preferred small molecules are biologically active in that they produce a biological effect in animals, preferably mammals, more preferably humans. Small molecules include, but are not limited to, radionuclides and imaging agents. In certain embodiments, the small molecule is a drug. Preferably, though not necessarily, the drug is one that has already been deemed safe and effective for use in humans or animals by the appropriate governmental agency or regulatory body. For example, drugs approved for human use are listed by the FDA under 21 C.F.R. §§ 330.5, 331 through 361, and 440 through 460, incorporated herein by reference; drugs for veterinary use are listed by the FDA under 21 C.F.R. §§ 500 through 589, incorporated herein by reference. All listed drugs are considered acceptable for use in accordance with the present disclosure. A “subject” to which administration is contemplated includes, but is not limited to, humans (i.e., a male or female of any age group, e.g., a pediatric subject (e.g., infant, child, adolescent) or adult subject (e.g., young adult, middle–aged adult, or senior adult)) and / or other non–human animals, for example, mammals (e.g., primates (e.g., cynomolgus monkeys, rhesus 11760147.1 monkeys); commercially relevant mammals such as cattle, pigs, horses, sheep, goats, cats, and / or dogs) and birds (e.g., commercially relevant birds such as chickens, ducks, geese, and / or turkeys). In certain embodiments, the animal is a mammal. The animal may be a male or female and at any stage of development. A non–human animal may be a transgenic animal. The term “patient” refers to a human subject in need of treatment of a disease or disorder. The term “biological sample” refers to any sample including tissue samples (such as tissue sections and needle biopsies of a tissue); cell samples (e.g., cytological smears (such as Pap or blood smears) or samples of cells obtained by microdissection); samples of whole organisms (such as samples of yeasts or bacteria); or cell fractions, fragments, organelles (such as obtained by lysing cells and separating the components thereof by centrifugation or otherwise). Other examples of biological samples include blood, serum, urine, semen, fecal matter, cerebrospinal fluid, interstitial fluid, mucus, tears, sweat, pus, biopsied tissue (e.g., obtained by a surgical biopsy or needle biopsy), nipple aspirates, milk, vaginal fluid, saliva, swabs (such as buccal swabs), or any material containing biomolecules that is derived from a first biological sample. Biological samples also include those biological samples that are transgenic, such as a transgenic oocyte, sperm cell, blastocyst, embryo, fetus, donor cell, or cell nucleus, or cells or cell lines derived from biological samples. The term “tissue” refers to any biological tissue of a subject (including a group of cells, a body part, or an organ) or a part thereof, including blood and / or lymph vessels, which is the object to which a compound, particle, and / or composition of the disclosure is delivered. A tissue may be an abnormal or unhealthy tissue, which may need to be treated. A tissue may also be a normal or healthy tissue that is under a higher than normal risk of becoming abnormal or unhealthy, which may need to be prevented. In certain embodiments, the tissue is the central nervous system. In certain embodiments, the tissue is the brain. The terms “administer,” “administering,” or “administration” refer to implanting, absorbing, ingesting, injecting, inhaling, or otherwise introducing a compound, or a pharmaceutical composition thereof. The terms “treatment,” “treat,” and “treating” refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of a “pathological condition” (e.g., a disease, disorder, or condition, or one or more signs or symptoms thereof) described herein. In some embodiments, treatment may be administered after one or more signs or symptoms have developed or have been observed. In other embodiments, treatment may be administered in the absence of signs or 11760147.1 symptoms of the disease or condition. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and / or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example, to delay or prevent recurrence. The terms “prevent,” “preventing,” or “prevention” refers to a prophylactic treatment of a subject who is not and was not with a disease or disorder but is at risk of developing the disease or disorder or who was with a disease or disorder, is not with the disease or disorder, but is at risk of regression of the disease or disorder. In certain embodiments, the subject is at a higher risk of developing the disease or disorder or at a higher risk of regression of the disease or disorder than an average healthy member of a population of subjects. The terms “condition,” “disease,” and “disorder” are used interchangeably. An “effective amount” of a compound described herein refers to an amount sufficient to elicit the desired biological response, i.e., treating the condition. As will be appreciated by those of ordinary skill in this art, the effective amount of a compound described herein may vary depending on such factors as the desired biological endpoint, the pharmacokinetics of the compound, the condition being treated, the mode of administration, and the age and health of the subject. An effective amount encompasses therapeutic and prophylactic treatment. For example, in treating cancer, an effective amount of a compound may reduce the tumor burden or stop the growth or spread of a tumor. A “therapeutically effective amount” of a compound described herein is an amount sufficient to provide a therapeutic benefit in the treatment of a condition or to delay or minimize one or more symptoms associated with the condition. A therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the treatment of the condition. The term “therapeutically effective amount” can encompass an amount that improves overall therapy, reduces, or avoids symptoms or causes of the condition, or enhances the therapeutic efficacy of another therapeutic agent. In certain embodiments, a therapeutically effective amount is an amount sufficient, e.g. for inhibiting a biological target (e.g., at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% inhibition of the target). In certain embodiments, a therapeutically effective amount is an amount sufficient for treating a disease or condition. 11760147.1 A “prophylactically effective amount” of a compound described herein is an amount sufficient to prevent a condition, or one or more signs or symptoms associated with the condition, or prevent its recurrence. A prophylactically effective amount of a compound means an amount of a therapeutic agent, alone or in combination with other agents, which provides a prophylactic benefit in the prevention of the condition. The term “prophylactically effective amount” can encompass an amount that improves overall prophylaxis or enhances the prophylactic efficacy of another prophylactic agent. The terms “therapeutic compound,” “therapeutic agent,” or “therapeutic moiety” refer to any substance having therapeutic properties that produce a desired, usually beneficial, effect. For example, therapeutic compounds, agents, and moieties may treat and / or ameliorate a disease or disorder. Therapeutic compounds, agents, and moieties, as disclosed herein, may be biologics or small molecule therapeutics, or combinations thereof. The term “sustained release” (also referred to as extended release or controlled release) refers to a continuous or continual release of a therapeutic agent introduced into the body of a subject over a period of time and at a therapeutic level sufficient to achieve a desired therapeutic effect throughout the period of time. The rate at which the therapeutic agent is released is slower than the rate of release of the therapeutic agent when it is administered alone or in a non- sustained release formulation. Sustained release formulations may, by way of example, be created as films, slabs, pellets, microparticles, microspheres, microcapsules, spheroids, shaped derivatives and paste. The formulations may be in a form that is suitable for suspension in isotonic saline, physiological buffer or other solution acceptable for injection into a patient. Further, the formulations may be used in conjunction with any implantable, insertable or injectable system that a person of ordinary skill would appreciate as useful in connection with embodiments herein including but not limited to parenteral formulations, microspheres, microcapsules, gels, pastes, implantable rods, pellets, plates or fibers, etc. BRIEF DESCRIPTION OF DRAWINGS FIGs.1A-1E show design of methyl-branched liposomes. FIG.1A shows the chemical structure of representative archaeal and eukaryotic lipids, and the methyl-branched lipid used here. FIG.1B shows schematic of methyl-branched liposomes for sustained release of TTX. FIG.1C shows cryogenic electron micrographs (Cryo-EM) of liposomes. FIG.1D shows 11760147.1 volume-weighted diameters of liposomes measured by dynamic light scattering. FIG.1E shows zeta potential of liposomes. Data are means ± s.d., n = 4. P > 0.05, not significant. FIGs.2A-2I show effect of branched liposomes on different payloads. FIG.2A shows the structure of sulforhodamine B (SRho). FIG.2B shows SRho loading in liposomes. FIG.2C shows cumulative release of SRho from different formulations at 37 °C. FIG.2D shows the structure of tetrodotoxin (TTX). FIG.2E shows TTX loading in liposomes. FIG.2F shows the cumulative release of TTX from different formulations at 37 °C. FIG.2G shows the structure of bupivacaine hydrochloride (Bup). FIG.2H shows Bup loading in liposomes. FIG.2I shows the cumulative release of Bup from different formulations at 37 °C. Data are means ± s.d., n = 4. In FIGs.2C, 2E, and 2I, p-values compare groups at 168 hours. FIGs.3A-3D show in vivo performance of TTX formulations. FIG.3A shows the duration of sensory nerve block from different formulations. Daggers indicate 100% mortality. Data are means ± s.d. n=4. p-value is from unpaired two-tailed t-test. **P = 0.001 comparing TTX@Lipo and TTX@Lipo-ME at 15 µg TTX. FIG.3B shows the frequency of block in the contralateral (uninjected) leg. FIG.3C shows the mortality from different formulations. FIG.3D shows sensory nerve block with different molar percentages of branched lipids in the liposomal formulation, using 25 µg TTX. Data are means ± s.d. n=4. FIGs.4A-4B show the retention and localization of liposomes. FIG.4A shows representative fluorescent in vivo imaging of rats injected with free Cy-5.5 or Cy5.5-conjugated liposomes. Fluorescence intensity is represented as radiant efficiency. Day 0 imaging was 30 min after injection. FIG.4B shows the quantification of the fluorescence intensity over time (as a percentage of fluorescence at Day 0), derived from data such as those in FIG.4A. Data are means ± s.d., n=4. P > 0.05 comparing Cy5.5-Lipo and Cy5.5-Lipo-ME five days after injection. FIGs.5A-5B show tissue reaction to formulations. H&E-stained sections of nerves and surrounding tissues (FIG.5A), and toluidine blue-stained section of nerves (FIG.5B). The scale bar is 200 μm for H&E-stained sections; 40 μm for toluidine blue. N = nerve, M = muscle, inf = inflammation. FIG.6 shows the stability of methyl-branched liposome size at 4°C over time. Data are means ± s.d., n = 4. FIG.7 shows the viscosity of different TTX formulations. FIGs.8A-8D show the characterizations of 100 nm liposomes. FIGs.8A-8B show the volume-weighted diameter of nanoscale liposomes by dynamic light scattering (DLS) (FIG.8A) 11760147.1 unmodified liposomes and (FIG.8B) methyl-branched liposomes. FIG.8C shows SRho loading in different nanoscale liposomes. FIG.8D shows the cumulative release of SRho from different formulations at 37°C. In FIGs.8C-8D data are the mean ± s.d., n = 4 independent experiments. Statistical analysis was performed using the two-tailed t-test. In d, the p-values compares groups at 96 hours. FIGs.9A-9B show Cytotoxicity of TTX formulations to (FIG.9A) myoblast C2C12 and (FIG.9B) pheochromocytoma PC12 cells. Data are means ± s.d., n = 4. P > 0.05 comparing different TTX formulations. FIG.10 shows the comparison of the durations of sensory and motor blocks from different TTX formulations. Data are means ± s.d., n = 4. FIG.11 shows H&E-stained sections of nerves and surrounding tissues from untreated rats, and toluidine blue-stained section of nerves from untreated rats at both low and high magnifications. N = nerve, M = muscle. FIG.12 shows H&E-stained sections of nerves and surrounding tissues at high magnification. The scale bar is 50 μm. N = nerve, M = muscle, inf = inflammation. FIG.13 shows toluidine blue-stained sections of sciatic nerves at high magnification. The scale bar is 10 μm. DETAILED DESCRIPTION Disclosed herein are liposome compositions useful as a depot for sustained drug delivery. The design of the compositions is inspired by the low permeability of Archaeal membranes to protons and solutes. Incorporating methyl-branched phospholipids into lipid bilayers decreased payload diffusion across liposomal membranes, thereby significantly enhancing drug load capacity and reducing the rate of release of diverse small molecules. As an in vivo demonstration of this approach, methyl-branched liposomes encapsulating the anesthetic tetrodotoxin (TTX) injected at the sciatic nerve achieved markedly prolonged local anesthesia for up to 70 hours, in comparison to the 16 hours achieved with liposomes containing conventional lipids. The present disclosure demonstrates the usefulness of liposomes comprising branched lipids (lipid of Formula (I)) to enhance liposomal depot systems for sustained drug delivery. The present disclosure provides a composition comprising a liposome encapsulating a therapeutic agent or a diagnostic agent, wherein the liposome comprises a lipid of Formula (I): 11760147.1 or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, wherein: m is an integer of 0-12; n is an integer of 0-12; x is an integer of 0-6; y is an integer of 0-6; R1is a phosphoglycerol, phosphocholine, phosphoethanolamine, or phosphoserine moiety; each R2is independently hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, -ORD1, -N(RD1a)2, -SRD1, -SO2, -NO2, -N3, or -CN, wherein at least one instance of R2is not hydrogen; each R3is independently hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, -ORD1, -N(RD1a)2, -SRD1, -SO2, -NO2, -N3, or -CN, wherein at least one instance of R3is not hydrogen; X1is C1-6alkylene; X2is C1-6 alkylene; wherein each RD1is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkynyl group, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and wherein each RD1ais independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted linear alkynyl, optionally substituted cycloalkynyl group, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen 11760147.1 protecting group; or optionally two instances of RD1aare taken together with their intervening atoms to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring. Liposome As described herein, the provided liposome comprises a lipid of Formula (I). In certain embodiments, the liposome is a synthetic liposome. In certain embodiments, the liposome comprises additional components. In certain embodiments, the liposome comprises a lipid of Formula (I), an anionic phospholipid, a zwitterionic phospholipid, and / or a sterol. Lipid of Formula (I) m and n As described herein, m is an integer of 0-12. In certain embodiments, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12. In certain embodiments, m is an integer of 1-12. In certain embodiments, m is an integer of 0-6. In certain embodiments, m is an integer of 6-12. In certain embodiments, m is an integer of 0-1. In certain embodiments, m is 0 or 1. In certain embodiments, m is 0. In certain embodiments, m is 1. In certain embodiments, m is 2. In certain embodiments, m is 3. In certain embodiments, m is 4. In certain embodiments, m is 5. In certain embodiments, m is 6. In certain embodiments, m is 7. In certain embodiments, m is 8. In certain embodiments, m is 9. In certain embodiments, m is 10. In certain embodiments, m is 11. In certain embodiments, m is 12. As described herein, n is an integer of 0-12. In certain embodiments, n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12. In certain embodiments, n is an integer of 1-12. In certain embodiments, n is an integer of 0-6. In certain embodiments, n is an integer of 6-12. In certain embodiments, n is an integer of 0-1. In certain embodiments, n is 0 or 1. In certain embodiments, n is 0. In certain embodiments, n is 1. In certain embodiments, n is 2. In certain embodiments, n is 3. In certain embodiments, n is 4. In certain embodiments, n is 5. In certain embodiments, n is 6. In certain embodiments, n is 7. In certain embodiments, n is 8. In certain embodiments, n is 9. In certain embodiments, n is 10. In certain embodiments, n is 11. In certain embodiments, n is 12. In certain embodiments, m is an integer of 0-12; and n is an integer of 0-12. In certain embodiments, m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12; and n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12. In certain embodiments, m is an integer of 1-12; and n is an integer of 1-12. In certain 11760147.1 embodiments, m is an integer of 0-6; and n is an integer of 0-6. In certain embodiments, m is an integer of 6-12; and n is an integer of 6-12. In certain embodiments, m is an integer of 0-1; and n is an integer of 0-1. In certain embodiments, m is 0 or 1; and n is 0 or 1. In certain embodiments, m and n are the same. In certain embodiments, m is 0; and n is 0. In certain embodiments, m is 1; and n is 1. In certain embodiments, m is 2; and n is 2. In certain embodiments, m is 3; and n is 3. In certain embodiments, m is 4; and n is 4. In certain embodiments, m is 5; and n is 5. In certain embodiments, m is 6; and n is 6. In certain embodiments, m is 7; and n is 7. In certain embodiments, m is 8; and n is 8. In certain embodiments, m is 9; and n is 9. In certain embodiments, m is 10; and n is 10. In certain embodiments, m is 11; and n is 11. In certain embodiments, m is 12; and n is 12. x and y As described herein, x is an integer of 0-6. In certain embodiments, x is 0, 1, 2, 3, 4, 5, or 6. In certain embodiments, x is an integer of 0-3. In certain embodiments, x is an integer of 1-3. In certain embodiments, x is 1 or 3. In certain embodiments, x is 0. In certain embodiments, x is 1. In certain embodiments, x is 2. In certain embodiments, x is 3. In certain embodiments, x is 4. In certain embodiments, x is 5. In certain embodiments, x is 6. As described herein, y is an integer of 0-6. In certain embodiments, y is 0, 1, 2, 3, 4, 5, or 6. In certain embodiments, y is an integer of 0-3. In certain embodiments, y is an integer of 1-3. In certain embodiments, y is 1 or 3. In certain embodiments, y is 0. In certain embodiments, y is 1. In certain embodiments, y is 2. In certain embodiments, y is 3. In certain embodiments, y is 4. In certain embodiments, y is 5. In certain embodiments, y is 6. In certain embodiments, x is an integer of 0-6; and y is an integer of 0-6. In certain embodiments, x is 0, 1, 2, 3, 4, 5, or 6; and y is 0, 1, 2, 3, 4, 5, or 6. In certain embodiments, x is an integer of 0-3; and y is an integer of 0-3. In certain embodiments, x is an integer of 1-3; and y is an integer of 1-3. In certain embodiments, x is 1 or 3; and y is 1 or 3. In certain embodiments, x and y are the same. In certain embodiments, x is 0; and y is 0. In certain embodiments, x is 1; and y is 1. In certain embodiments, x is 2; and y is 2. In certain embodiments, x is 3; and y is 3. In certain embodiments, x is 4; and y is 4. In certain embodiments, x is 5; and y is 5. In certain embodiments, x is 6; and y is 6. R111760147.1 As described herein, R1is a phosphoglycerol, phosphocholine, phosphoethanolamine, phosphoinositol, or phosphoserine moiety. In certain embodiments, R1is an unsubstituted phosphoglycerol, unsubstituted phosphocholine, unsubstituted phosphoethanolamine, unsubstituted phosphoinositol, or unsubstituted phosphoserine moiety. In certain embodiments, R1is a phosphoglycerol moiety. In certain embodiments, R1is an unsubstituted phosphoglycerol moiety. In certain embodiments, R1is a phosphocholine moiety. In certain embodiments, R1is an unsubstituted phosphocholine moiety. In certain embodiments, R1is a phosphoethanolamine moiety. In certain embodiments, R1is an unsubstituted phosphoethanolamine moiety. In certain embodiments, R1is a phosphoinositol moiety. In certain embodiments, R1is an unsubstituted phosphoinositol moiety. In certain embodiments, R1is a phosphoserine moiety. In certain embodiments, R1is an unsubstituted phosphoserine moiety. occurrence of RAis independently hydrogen or unsubstituted alkyl; each occurrence of RA1is independently hydrogen, unsubstituted alkyl, or an oxygen protecting group; and z is 1, 2, 3, 4, 5, or 6. In certain embodiments, each occurrence of RAis independently hydrogen or unsubstituted alkyl; and z is 1, 2, 3, 4, 5, or 6. In certain embodiments, each occurrence of RAis independently hydrogen or unsubstituted alkyl; and z is 2. In certain embodiments, 11760147.1 R2and R3As described herein, each R2is independently hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, -ORD1, -N(RD1a)2, -SRD1, -SO2, -NO2, -N3, or -CN, wherein at least one instance of R2is not hydrogen; wherein each RD1is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkynyl group, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and wherein each RD1ais independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted linear alkynyl, optionally substituted cycloalkynyl group, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two instances of RD1aare taken together with their intervening atoms to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring. In certain embodiments, each R2is independently hydrogen, optionally substituted alkyl, or optionally substituted aryl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, unsubstituted alkyl, or unsubstituted aryl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, optionally substituted C1-6alkyl, or optionally substituted aryl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, unsubstituted C1-6 alkyl, or unsubstituted aryl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, optionally substituted C1-6alkyl, or optionally substituted phenyl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, unsubstituted C1-6 alkyl, or unsubstituted phenyl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, optionally substituted C1-4alkyl, or optionally substituted phenyl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, unsubstituted C1-4 alkyl, or unsubstituted phenyl, wherein at 11760147.1 least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, optionally substituted C1-3 alkyl, or optionally substituted phenyl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, unsubstituted C1-3alkyl, or unsubstituted phenyl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, optionally substituted C1- 2 alkyl, or optionally substituted phenyl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, unsubstituted C1-2alkyl, or unsubstituted phenyl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, methyl, -CH2OPh, ethyl, or phenyl, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen, methyl, ethyl, or phenyl, w herein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen or -CH2OPh, wherein at least one instance of R2is not hydrogen. In certain embodiments, each R2is independently hydrogen or -CH2OPh, wherein one instance of R2is not hydrogen. In certain embodiments, each R2is independently optionally substituted alkyl or optionally substituted aryl. In certain embodiments, each R2is independently optionally substituted C1-6alkyl or optionally substituted phenyl. In certain embodiments, each R2is independently unsubstituted C1-6 alkyl or unsubstituted phenyl. In certain embodiments, each R2is independently unsubstituted C1-4 alkyl or unsubstituted phenyl. In certain embodiments, each R2is independently unsubstituted C1-3alkyl or unsubstituted phenyl. In certain embodiments, each R2is independently unsubstituted C1-2alkyl or unsubstituted phenyl. In certain embodiments, each R2is independently methyl, ethyl, or phenyl. In certain embodiments, each R2is independently optionally substituted alkyl. In certain embodiments, each R2is independently optionally substituted C1-6alkyl. In certain embodiments, each R2is independently optionally substituted C1-4 alkyl. In certain embodiments, each R2is independently optionally substituted C1-3 alkyl. In certain embodiments, each R2is independently optionally substituted C1-2alkyl. In certain embodiments, each R2is independently unsubstituted C1-6 alkyl. In certain embodiments, each R2is independently unsubstituted C1-4 alkyl. In certain embodiments, each R2is independently unsubstituted C1-3alkyl. In certain embodiments, each R2is independently unsubstituted C1-2alkyl. In certain embodiments, each R2is ethyl. In certain embodiments, each R2is methyl. 11760147.1 R3In certain embodiments, each R3is independently optionally substituted aryl. In certain embodiments, each R3is independently optionally substituted phenyl. In certain embodiments, each R3is unsubstituted phenyl. As described herein, each R3is independently hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, -ORD1, -N(RD1a)2, -SRD1, -SO2, -NO2, -N3, or -CN, wherein at least one instance of R2is not hydrogen; wherein each RD1is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkynyl group, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and wherein each RD1ais independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted linear alkynyl, optionally substituted cycloalkynyl group, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two instances of RD1aare taken together with their intervening atoms to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring. In certain embodiments, each R3is independently hydrogen, optionally substituted alkyl, or optionally substituted aryl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, unsubstituted alkyl, or unsubstituted aryl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, optionally substituted C1-6 alkyl, or optionally substituted aryl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, unsubstituted C1-6alkyl, or unsubstituted aryl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, optionally substituted C1-6 alkyl, or optionally substituted phenyl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, unsubstituted C1-6alkyl, or unsubstituted phenyl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, optionally substituted C1-4 alkyl, or optionally 11760147.1 substituted phenyl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, unsubstituted C1-4 alkyl, or unsubstituted phenyl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, optionally substituted C1-3alkyl, or optionally substituted phenyl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, unsubstituted C1-3 alkyl, or unsubstituted phenyl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, optionally substituted C1-2 alkyl, or optionally substituted phenyl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, unsubstituted C1-2 alkyl, or unsubstituted phenyl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, methyl, -CH2OPh, ethyl, or unsubstituted phenyl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen, methyl, ethyl, or phenyl, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen or - CH2OPh, wherein at least one instance of R3is not hydrogen. In certain embodiments, each R3is independently hydrogen or -CH2OPh, wherein one instance of R3is not hydrogen. In certain embodiments, each R3is independently optionally substituted alkyl or optionally substituted aryl. In certain embodiments, each R3is independently optionally substituted C1-6 alkyl or optionally substituted phenyl. In certain embodiments, each R3is independently unsubstituted C1-6alkyl or unsubstituted phenyl. In certain embodiments, each R3is independently unsubstituted C1-4alkyl or unsubstituted phenyl. In certain embodiments, each R3is independently unsubstituted C1-3 alkyl or unsubstituted phenyl. In certain embodiments, each R3is independently unsubstituted C1-2alkyl or unsubstituted phenyl. In certain embodiments, each R3is independently methyl, ethyl, or unsubstituted phenyl. In certain embodiments, each R3is independently optionally substituted alkyl. In certain embodiments, each R3is independently optionally substituted C1-6 alkyl. In certain embodiments, each R3is independently optionally substituted C1-4alkyl. In certain embodiments, each R3is independently optionally substituted C1-3 alkyl. In certain embodiments, each R3is independently optionally substituted C1-2 alkyl. In certain embodiments, each R3is independently unsubstituted C1-6alkyl. In certain embodiments, each R3is independently unsubstituted C1-4 alkyl. In certain embodiments, each R3is independently 11760147.1 unsubstituted C1-3alkyl. In certain embodiments, each R3is independently unsubstituted C1-2alkyl. In certain embodiments, each R3is ethyl. In certain embodiments, each R2is methyl. In certain embodiments, each R3is independently optionally substituted aryl. In certain embodiments, each R3is independently optionally substituted phenyl. In certain embodiments, each R3is unsubstituted phenyl. R2and R3In certain embodiments, R2and R3are different. In certain embodiments, R2and R3are the same. In certain embodiments, R2and R3are methyl, ethyl, or unsubstituted phenyl. In certain embodiments, R2and R3are methyl. In certain embodiments, R2and R3are ethyl. In certain embodiments, R2and R3are unsubstituted phenyl. In certain embodiments, one instance of R2is -CH2OPh, one instance of R3is -CH2OPh, and the remaining instances of R2and R3are hydrogen. X1As described herein, X1is substituted or unsubstituted C1-6 alkylene. In certain embodiments, X1is unsubstituted C1-6alkylene. In certain embodiments, X1is unsubstituted C1-4alkylene. In certain embodiments, X1is unsubstituted C1-3 alkylene. In certain embodiments, X1is unsubstituted C2-4 alkylene. In certain embodiments, X1is unsubstituted propylene. Y1As described herein, Y1is substituted or unsubstituted C1-6 alkylene. In certain embodiments, Y1is unsubstituted C1-6alkylene. In certain embodiments, Y1is unsubstituted C1-4alkylene. In certain embodiments, Y1is unsubstituted C1-3alkylene. In certain embodiments, Y1is unsubstituted C2-4 alkylene. In certain embodiments, Y1is unsubstituted propylene. X1and Y1In certain embodiments, X1and Y1are different. In certain embodiments, X1and Y1are the same. In certain embodiments, X1and Y1are each independently unsubstituted C1-6 alkylene. In certain embodiments, X1and Y1are each independently unsubstituted C1-4alkylene. In certain embodiments, X1and Y1are each independently unsubstituted C1-3 alkylene. In certain 11760147.1 embodiments, X1and Y1are each independently unsubstituted C2-4alkylene. In certain embodiments, X1and Y1are each unsubstituted propylene. Embodiments of Formula (I) In certain embodiments, the lipid of Formula (I) is of Formula (I-a): or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, wherein R1, R2, R3, x, and y are as defined herein. In certain embodiments, the lipid of Formula (I) is of Formula (I-a-1): or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, wherein R2, R3, x, and y are as defined herein. In certain embodiments, the lipid of Formula (I) is of Formula (I-a-2): or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, wherein R2and R3are as defined herein. In certain embodiments, the lipid of Formula (I) is of Formula (I-b): or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, wherein R1, R2, and R3are as defined herein, p is an integer of 8-20; 11760147.1 and q is an integer of 8-20. In certain embodiments, p is an integer of 10-20, 10-15, 12-15, or 12-14. In certain embodiments, q is an integer of 10-20, 10-15, 12-15, or 12-14. In certain embodiments, p and q are the same. In certain embodiments, the lipid of Formula (I) is of Formula (I-b-1): or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, wherein R1, R2, and R3are as defined herein, p is an integer of 8-20; and q is an integer of 8-20. In certain embodiments, p is an integer of 10-20, 10-15, 12-15, or 12-14. In certain embodiments, q is an integer of 10-20, 10-15, 12-15, or 12-14. In certain embodiments, p and q are the same. In certain embodiments, the lipid of Formula (I) is of Formula (I-b-2): or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, wherein R2and R3are as defined herein. In certain embodiments, the lipid of Formula (I) is of formula: 11760147.1 or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: 11760147.1 or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: 11760147.1 or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: 11760147.1 or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. 11760147.1 In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the lipid of Formula (I) is of formula: 11760147.1 or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the liposome comprises, by mol%, about 1% to about 100%, about 50% to about 100%, about 25% to about 100%, about 1% to about 99%, about 5% to about 97%, about 5% to about 95%, about 5% to about 90%, about 5% to about 80%, about 5% to about 70%, about 5% to about 60%, about 5% to about 50%, about 25% to about 50%, about 35% to about 90%, about 25% to about 30%, about 25% to about 35%, about 27% to about 32%, about 26% to about 28%, about 40% to about 60%, about 45% to about 55%, about 48% to about 52%, about 5% to about 15%, about 8% to about 12%, about 10%, about 27%, about 27.3%, about 30%, about 50%, or about 100% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 10%, about 27%, about 27.3%, about 30%, about 50%, or about 100% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 10% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 27% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 27.3% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 30% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 50% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 100% of the lipid of Formula (I), or a salt, co-crystal, 11760147.1 tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, with respect to the total molar mass of the liposome. Anionic Phospholipid In certain embodiments, the liposome comprises an anionic phospholipid. An anionic phospholipid is a phospholipid that possesses an overall negative charge at physiological pH. The anionic phospholipid includes salts of the phospholipid. In certain embodiments, the anionic phospholipid is a phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidic acid (PA), diphosphatidylglycerol (DPG ) or cardiolipin (CL), or a derivative or mixture thereof. In certain embodiments, the anionic phospholipid is a phosphatidylglycerol. In certain embodiments, the anionic phospholipid is 1,2-distearoyl-sn-glycero-3- phosphatidylglycerol (DSPG), 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG), 1,2- dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG), 1,2-dilauroyl-sn-glycero-3-phospho-L- serine (DSPS), 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS), 1,2-dimyristoyl-sn- glycero-3-phospho-L-serine (DMPS), 1,2-distearoyl-sn-glycero-3-phosphate (DSPA), 1,2- dipalmitoyl-sn-glycero-3-phosphate (DPPA), or 1,2-dimyristoyl-sn-glycero-3-phosphate (DMPA), or mixture thereof. In certain embodiments, the anionic phospholipid is 1,2-distearoyl- sn-glycero-3-phosphatidylglycerol (DSPG). In certain embodiments, the liposome comprises, by mol%, about 1% to about 25%, about 1% to about 20%, about 10% to about 20%, about 15% to about 20%, about 16% to about 20%, about 18%, or about 18.2% of the anionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 18% of the anionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 18.2% of the anionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by weight, about 1% to about 25%, about 1% to about 20%, about 10% to about 20%, about 15% to about 20%, about 16% to about 20%, about 18%, or about 18.2% of a phosphatidylglycerol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 18% of a phosphatidylglycerol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 18.2% of a phosphatidylglycerol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 1% to about 25%, 11760147.1 about 1% to about 20%, about 10% to about 20%, about 15% to about 20%, about 16% to about 20%, about 18%, or about 18.2% DSPG with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 18% or about 18.2% DSPG with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 18% DSPG with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 18.2% DSPG with respect to the total molar mass of the liposome. Zwitterionic Phospholipid In certain embodiments, the liposome comprises a zwitterionic phospholipid. A zwitterionic phospholipid is a phospholipid that possesses a negatively charged moiety and a positively charged moiety at physiological pH such that the phospholipid has an overall neutral charge at physiological pH. The zwitterionic phospholipid includes salts of the phospholipid. In certain embodiments, the zwitterionic phospholipid is a phosphatidylethanolamine (PE) or a phosphatidylcholine (PC), or a derivative or mixture thereof. In certain embodiments, the zwitterionic phospholipid is a phosphatidylcholine. In certain embodiments, the zwitterionic phospholipid is 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE), 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine, or 1,2- dipalmitoleoyl-sn-glycero-3-phosphoethanolamine, or mixture thereof. In certain embodiments, the anionic phospholipid is 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). In certain embodiments, the liposome comprises, by mol%, about 1% to about 50%, about 1% to about 35%, about 1% to about 30%, about 1% to about 20%, about 1% to about 10%, about 1% to about 5%, about 3% to about 7%, about 4% to about 6%, about 20% to about 30%, about 23% to about 27%, about 24% to about 26%, about 25% to about 30%, about 26% to about 28%, about 40% to about 50%, about 44% to about 46%, about 4%, about 4.5%, about 5%, about 25%, about 27%, about 27.3%, about 44%, about 44.5%, or about 45% of the zwitterionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 4% of the zwitterionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 4.5% of the zwitterionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 5% of the zwitterionic phospholipid with respect to the total molar mass of the liposome. In certain 11760147.1 embodiments, the liposome comprises, by mol%, about 25% of the zwitterionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 27% of the zwitterionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 27.3% of the zwitterionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 44% of the zwitterionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 44.5% of the zwitterionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 45% of the zwitterionic phospholipid with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 1% to about 50%, about 1% to about 35%, about 1% to about 30%, about 1% to about 20%, about 1% to about 10%, about 1% to about 5%, about 3% to about 7%, about 4% to about 6%, about 20% to about 30%, about 23% to about 27%, about 24% to about 26%, about 25% to about 30%, about 26% to about 28%, about 40% to about 50%, about 44% to about 46%, about 4%, about 4.5%, about 5%, about 25%, about 27%, about 27.3%, about 44%, about 44.5%, or about 45% of a phosphatidylcholine with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 4% of a phosphatidylcholine with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 4.5% of a phosphatidylcholine with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 5% of a phosphatidylcholine with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 25% of a phosphatidylcholine with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 27% of a phosphatidylcholine with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 27.3% of a phosphatidylcholine with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 44% of a phosphatidylcholine with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 44.5% of a phosphatidylcholine with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 45% of a phosphatidylcholine with respect to the total molar mass of the liposome. 11760147.1 In certain embodiments, the liposome comprises, by mol%, about 1% to about 50%, about 1% to about 35%, about 1% to about 30%, about 1% to about 20%, about 1% to about 10%, about 1% to about 5%, about 3% to about 7%, about 4% to about 6%, about 20% to about 30%, about 23% to about 27%, about 24% to about 26%, about 25% to about 30%, about 26% to about 28%, about 40% to about 50%, about 44% to about 46%, about 4%, about 4.5%, about 5%, about 25%, about 27%, about 27.3%, about 44%, about 44.5%, or about 45% DOPC with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 4%, about 4.5%, about 5%, about 25%, about 27%, about 27.3%, about 44%, about 44.5%, or about 45% DOPC with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 4% DOPC with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 4.5% DOPC with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 5% DOPC with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 25% DOPC with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 27% DOPC with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 27.3% DOPC with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 44% DOPC with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 44.5% DOPC with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 45% DOPC with respect to the total molar mass of the liposome. Sterol In certain embodiments, the liposome comprises a sterol. A sterol is an organic compound with formula C17H28O and is derived from gonane by replacement of a hydrogen atom in position 3 of the A-ring by a hydroxyl group. The sterol includes salts of the sterol. In certain embodiments, the sterol is cholesterol, a cholesterol derivative (e.g., cholesterol- phosphocholine, cholesterolpolyethyleneglycol, cholesterol-S04), a cholesteryl ester, vitamin D, or a phytosterol (e.g., sitosterol, campesterol, stigmasterol), or mixture thereof. In certain embodiments, the sterol is cholesterol, desmosterol, lanosterol, zymosterol, ergosterol, stigmasterol, or campestanol. In certain embodiments, the sterol is cholesterol. 11760147.1 In certain embodiments, the liposome comprises, by mol%, about 1% to about 25%, about 1% to about 20%, about 10% to about 20%, about 15% to about 20%, about 16% to about 20%, about 18%, or about 18.2% of the sterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 18% of the sterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 18.2% of the sterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 1% to about 25%, about 1% to about 20%, about 10% to about 20%, about 15% to about 20%, about 16% to about 20%, about 18%, or about 18.2% cholesterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 18% cholesterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 18.2% cholesterol with respect to the total molar mass of the liposome. Embodiments of the Liposome In certain embodiments, the liposome comprises, by mol%, about 50% the lipid of Formula (I), about 18% DSPG, about 5% DOPC, and about 27% cholesterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 50% the lipid of Formula (I), about 18.2% DSPG, about 4.5% DOPC, and about 27.3% cholesterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 27% the lipid of Formula (I), about 18% DSPG, about 27% DOPC, and about 27% cholesterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 27.3% the lipid of Formula (I), about 18.2% DSPG, about 27.3% DOPC, and about 27.3% cholesterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 30% the lipid of Formula (I), about 18% DSPG, about 25% DOPC, and about 27% cholesterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 30% the lipid of Formula (I), about 18.2% DSPG, about 24.5% DOPC, and about 27.3% cholesterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 10% the lipid of Formula (I), about 18% DSPG, about 45% DOPC, and about 27% cholesterol with respect to the total molar mass of the liposome. In certain embodiments, the liposome comprises, by mol%, about 10% the 11760147.1 lipid of Formula (I), about 18.2% DSPG, about 44.5% DOPC, and about 27.3% cholesterol with respect to the total molar mass of the liposome. Diagnostic Agent In certain embodiments, the liposome encapsulates a diagnostic agent. In certain embodiments, the diagnostic agent is a fluorophore. In certain embodiments, the diagnostic agent is a small molecule or a biologic. In certain embodiments, the diagnostic agent is a small molecule. In certain embodiments, the diagnostic agent is conjugated to a protein, a polymer, or a small molecule. In certain embodiments, the diagnostic agent is conjugated to the liposome. In certain embodiments, the diagnostic agent is Cy-5.5. In certain embodiments, the diagnostic agent is Sulforhodamine B, Cy-5.5, indocyanine green, fluorescein isothiocyanate, methylene blue, or coumarin. In certain embodiments, the diagnostic agent is Sulforhodamine B. In certain embodiments, the diagnostic agent comprises, by weight, about 0.05% to about 10% of the total mass of the composition. In certain embodiments, the diagnostic agent comprises, by weight, about 0.05% to about 0.2%, about 0.1% to about 0.2%, about 0.12% to about 0.2%, about 0.13% to about 0.2%, about 0.14% to about 0.2%, about 0.15% to about 0.2%, about 0.15%, or about 0.16% of the total mass of the composition. In certain embodiments, the diagnostic agent comprises, by weight, about 2% to about 4%, about 2.5% to about 3.5%, about 2% to about 3%, about 2.8% to about 3.2%, about 2.8% to about 3.0%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, or about 0.16% of the total mass of the composition. In certain embodiments, the amount of the diagnostic agent in the composition is about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 40%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% greater than the amount of the diagnostic agent in a composition without the lipid of Formula (I). Therapeutic Agent In certain embodiments, the liposome encapsulates a therapeutic agent. In certain embodiments, the liposome does not encapsulate a diagnostic agent. In certain embodiments, the therapeutic agent is a small molecule or a biologic. In certain embodiments, the therapeutic 11760147.1 agent is a small molecule, a protein, or a nucleic acid. In certain embodiments, the therapeutic agent is a small molecule. In certain embodiments, the therapeutic agent is an anesthetic. In certain embodiments, the therapeutic agent is a local anesthetic (e.g., tetrodotoxin, saxitoxin, neosaxitoxin, bupivacaine, amylocaine, ambucaine, articaine, benzocaine, benzonatate, butacaine, butanilicaine, carbocaine, cepastat, chloraseptic, chloroprocaine, cinchocaine, citanest, cyclomethycaine, dibucaine, diperodon, dimethocaine, eucaine, etidocaine, fomocaine, fotocaine, hydroxyprocaine, isobucaine, levobupivacaine, lidocaine, marcaine, mepivacaine, meprylcaine, metabutoxycaine, nitracaine, orthocaine, orabloc, oxetacaine, oxybuprocaine, paraethoxycaine, phenacaine, piperocaine, piridocaine, polocaine, posimir, pramocaine, prilocaine, primacaine, procaine, procainamide, proparacaine, propoxycaine, pyrrocaine, quinisocaine, ropivacaine, sensorcaine, septocaine, trimecaine, tetracaine, tolycaine, tropacocaine, ulcerease, xylocaine, or zorcaine). In certain embodiments, the therapeutic agent is a local anesthetic compound, for example, but not limited to, an amino ester compound (e.g., procaine, tetracaine, chloroprocaine, benzocaine, butacaine, dimethocaine) or an amino amide compound (e.g., procainamide, lidocaine). In certain embodiments, the local anesthetic is a sodium channel blocker, for example, a site 1 sodium channel blocker (e.g., tetrodotoxin, saxitoxins (saxitoxin, neosaxitoxin), gonyautoxins (gonyautoxin V, gonyautoxin VI), µ-conotoxins)) or an amino amide local anesthetic. In certain embodiments, the therapeutic agent is a site 1 sodium channel blocker, amino ester anesthetic, or an amino amide anesthetic, or a derivative thereof. In certain embodiments, the therapeutic agent is tetrodotoxin, saxitoxin, neosaxitoxin, bupivacaine, amylocaine, ambucaine, articaine, benzocaine, benzonatate, butacaine, butanilicaine, carbocaine, cepastat, chloraseptic, chloroprocaine, cinchocaine, citanest, cyclomethycaine, dibucaine, diperodon, dimethocaine, eucaine, etidocaine, fomocaine, fotocaine, hydroxyprocaine, isobucaine, levobupivacaine, lidocaine, marcaine, mepivacaine, meprylcaine, metabutoxycaine, nitracaine, orthocaine, orabloc, oxetacaine, oxybuprocaine, paraethoxycaine, phenacaine, piperocaine, piridocaine, polocaine, posimir, pramocaine, prilocaine, primacaine, procaine, procainamide, proparacaine, propoxycaine, pyrrocaine, quinisocaine, ropivacaine, sensorcaine, septocaine, trimecaine, tetracaine, tolycaine, tropacocaine, ulcerease, xylocaine, zorcaine, decarbamoyl saxitoxin, gonyautoxins, or derivatives thereof. In certain embodiments, the therapeutic agent is tetrodotoxin or bupivacaine. 11760147.1 In certain embodiments, the therapeutic agent is tetrodotoxin. In certain embodiments, the therapeutic agent is bupivacaine. In certain embodiments, the composition comprises an effective amount of the therapeutic agent. In certain embodiments, the composition comprises a therapeutically effective amount of the therapeutic agent. In certain embodiments, the composition comprises a prophylactically effective amount of the therapeutic agent. In certain embodiments, the effective amount is an amount effective for treating a disease or disorder that would benefit from administration of a therapeutic agent in a subject in need thereof. In certain embodiments, the effective amount is an amount effective for preventing a disease or disorder that would benefit from administration of a therapeutic agent in a subject in need thereof. In certain embodiments, the effective amount is an amount effective for reducing the risk of developing a disease or disorder that would benefit from administration of a therapeutic agent in a subject in need thereof. In certain embodiments, the therapeutic agent comprises, by weight, about 0.05% to about 10% of the total mass of the composition. In certain embodiments, the therapeutic agent comprises, by weight, about 0.05% to about 0.2%, about 0.1% to about 0.2%, about 0.12% to about 0.2%, about 0.13% to about 0.2%, about 0.14% to about 0.2%, about 0.15% to about 0.2%, about 0.15%, or about 0.16% of the total mass of the composition. In certain embodiments, the therapeutic agent comprises, by weight, about 2% to about 4%, about 2.5% to about 3.5%, about 2% to about 3%, about 2.8% to about 3.2%, about 2.8% to about 3.0%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, or about 0.16% of the total mass of the composition. In certain embodiments, the amount of the therapeutic agent in the composition is about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 40%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% greater than the amount of the therapeutic agent in a composition without the lipid of Formula (I). Embodiments of the composition In certain embodiments, the composition is characterized in that, when tested in vitro by placing the composition in a medium, less than 100%, less than 90%, less than 80%, less than 11760147.1 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 168 hours after placing the composition in the medium. In certain embodiments, the composition is characterized in that, when tested in vitro by placing the composition in a medium, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 144 hours after placing the composition in the medium. In certain embodiments, the composition is characterized in that, when tested in vitro by placing the composition in a medium, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 120 hours after placing the composition in the medium. In certain embodiments, the composition is characterized in that, when tested in vitro by placing the composition in a medium, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 96 hours after placing the composition in the medium. In certain embodiments, the composition is characterized in that, when tested in vitro by placing the composition in a medium, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 72 hours after placing the composition in the medium. In certain embodiments, the composition is characterized in that, when tested in vitro by placing the composition in a medium, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 48 hours after placing the composition in the medium. In certain embodiments, the composition is characterized in that, when tested in vitro by placing the composition in a medium, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 24 hours after placing the composition in the medium. In certain embodiments, the composition is characterized in that, when tested in vitro by placing the composition in a medium, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 12 hours after placing the composition in the medium. In certain embodiments, 11760147.1 the composition is characterized in that, when tested in vitro by placing the composition in a medium, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 6 hours after placing the composition in the medium. In certain embodiments, the composition is characterized in that, when tested in vitro by placing the composition in a medium, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 3 hours after placing the composition in the medium. In certain embodiments, the medium is physiological saline or phosphate-buffered saline (PBS) having a pH of about 7.4. In certain embodiments, the composition is characterized in that, when administered to a subject, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 168 hours after administration of the composition. In certain embodiments, the composition is characterized in that, when administered to a subject, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 144 hours after administration of the composition. In certain embodiments, the composition is characterized in that, when administered to a subject, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 120 hours after administration of the composition. In certain embodiments, the composition is characterized in that, when administered to a subject, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 96 hours after administration of the composition. In certain embodiments, the composition is characterized in that, when administered to a subject, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 72 hours after administration of the composition. In certain embodiments, the composition is characterized in that, when administered to a subject, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the 11760147.1 therapeutic agent is released from the composition 48 hours after administration of the composition. In certain embodiments, the composition is characterized in that, when administered to a subject, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 24 hours after administration of the composition. In certain embodiments, the composition is characterized in that, when administered to a subject, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 12 hours after administration of the composition. In certain embodiments, the composition is characterized in that, when administered to a subject, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 6 hours after administration of the composition. In certain embodiments, the composition is characterized in that, when administered to a subject, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 3 hours after administration of the composition. In certain embodiments, the composition is characterized in that, when administered to a subject, duration of a therapeutic effect is extended by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, or at least 200% compared to duration of the therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the therapeutic effect is nerve block and / or reduced pain. In certain embodiments, the therapeutic effect is nerve block. In certain embodiments, the therapeutic effect is reduced pain. Pharmaceutical Compositions, Kits, and Administration The present disclosure provides compositions comprising a liposome encapsulating a therapeutic agent. In certain embodiments, the composition is a pharmaceutical composition. In 11760147.1 certain embodiments, the composition further comprises a pharmaceutically acceptable excipient. In certain embodiments, the pharmaceutical composition comprises an effective amount of a therapeutic agent. In certain embodiments, the effective amount is a therapeutically effective amount. In certain embodiments, the effective amount is a prophylactically effective amount. In certain embodiments, the effective amount is an amount effective for treating a disease or condition in a subject in need thereof. In certain embodiments, the effective amount is an amount effective for preventing a disease or condition in a subject in need thereof. In certain embodiments, the effective amount is an amount effective for reducing the risk of developing a disease or condition in a subject in need thereof. Compositions described herein can be prepared by any method known in the art of pharmacology. In general, such preparatory methods include the steps of bringing the therapeutic agent into association with the liposome such that the therapeutic agent is encapsulated within the liposome. In certain embodiments, the preparation further comprises adding and / or one or more other accessory ingredients, and then, if necessary and / or desirable, shaping and / or packaging the product into a desired single- or multi-dose unit. Pharmaceutical compositions can be prepared, packaged, and / or sold in bulk, as a single unit dose, and / or as a plurality of single unit doses. As used herein, a “unit dose” is a discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject and / or a convenient fraction of such a dosage, such as, for example, one-half or one-third of such a dosage. The compositions provided herein can be administered by any route, including enteral (e.g., oral), parenteral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, interdermal, rectal, intravaginal, intraperitoneal, topical, mucosal, nasal, bucal, sublingual; by intratracheal instillation, bronchial instillation, and / or inhalation; and / or as an oral spray, nasal spray, and / or aerosol. A composition, as described herein, can be administered in combination with one or more additional agents (e.g., pharmaceutical agent, e.g., therapeutically and / or prophylactically active agents). The compositions can be administered in combination with additional pharmaceutical agents that improve their activity (e.g., activity (e.g., potency and / or efficacy) in treating a disease in a subject in need thereof, in preventing a disease in a subject in need 11760147.1 thereof, and / or in reducing the risk to develop a disease in a subject in need thereof), improve bioavailability, improve their ability to cross the blood-brain barrier, improve safety, reduce drug resistance, reduce and / or modify metabolism, inhibit excretion, and / or modify distribution in a subject or cell. It will also be appreciated that the therapy employed may achieve a desired effect for the same disorder, and / or it may achieve different effects. In certain embodiments, a pharmaceutical composition described herein including a therapeutic agent described herein and an additional agent exhibits a synergistic effect that is absent in a pharmaceutical composition including one of the therapeutic agent and the additional agent, but not both. In certain embodiments, the additional agent is a therapeutic agent. The composition can be administered concurrently with, prior to, or subsequent to one or more additional pharmaceutical agents, which may be useful as, e.g., combination therapies. Pharmaceutical agents include therapeutically active agents. Pharmaceutical agents also include prophylactically active agents. Pharmaceutical agents include small organic molecules such as drug compounds (e.g., compounds approved for human or veterinary use by the U.S. Food and Drug Administration as provided in the Code of Federal Regulations (CFR)), peptides, proteins, carbohydrates, monosaccharides, oligosaccharides, polysaccharides, nucleoproteins, mucoproteins, lipoproteins, synthetic polypeptides or proteins, small molecules linked to proteins, glycoproteins, steroids, nucleic acids, DNAs, RNAs, nucleotides, nucleosides, oligonucleotides, antisense oligonucleotides, lipids, hormones, vitamins, and cells. Each additional pharmaceutical agent may be administered at a dose and / or on a time schedule determined for that pharmaceutical agent. The additional pharmaceutical agents may also be administered together with each other and / or with the compound or composition described herein in a single dose or administered separately in different doses. The particular combination to employ in a regimen will take into account compatibility of the compound described herein with the additional pharmaceutical agent(s) and / or the desired therapeutic and / or prophylactic effect to be achieved. In general, it is expected that the additional pharmaceutical agent(s) in combination be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in combination will be lower than those utilized individually. In certain embodiments, the subject is an animal. The animal may be of either sex and may be at any stage of development. In certain embodiments, the subject described herein is a human. In certain embodiments, the subject is a non-human animal. In certain embodiments, the 11760147.1 subject is a mammal. In certain embodiments, the subject is a non-human mammal. In certain embodiments, the subject is a domesticated animal, such as a dog, cat, cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a companion animal, such as a dog or cat. In certain embodiments, the subject is a livestock animal, such as a cow, pig, horse, sheep, or goat. In certain embodiments, the subject is a zoo animal. In another embodiment, the subject is a research animal, such as a rodent (e.g., mouse, rat), dog, pig, or non-human primate. In certain embodiments, the animal is a genetically engineered animal. In certain embodiments, the animal is a transgenic animal (e.g., transgenic mice and transgenic pigs). In certain embodiments, the subject is a fish or reptile. Also encompassed by the disclosure are kits (e.g., pharmaceutical packs). The kits provided comprise a composition described herein and instructions for using the kit. The kits provided may comprise a composition described herein and a container (e.g., a vial, ampule, bottle, syringe, and / or dispenser package, or other suitable container). In some embodiments, provided kits may optionally further include a second container comprising a pharmaceutical excipient for dilution or suspension of a composition described herein. In some embodiments, the composition described herein provided in the first container and the second container are combined to form one unit dosage form. Thus, in one aspect, provided are kits including a first container comprising a composition described herein. In certain embodiments, the kits are useful for treating a disease or condition (e.g., pain) in a subject in need thereof. In certain embodiments, the kits are useful for preventing a disease or condition (e.g., pain) in a subject in need thereof. In certain embodiments, the kits are useful for reducing the risk of developing a disease or condition (e.g., pain) in a subject in need thereof. A kit described herein may also include information as required by a regulatory agency such as the U.S. Food and Drug Administration (FDA). In certain embodiments, the information included in the kits is prescribing information. In certain embodiments, a kit described herein may include one or more additional pharmaceutical agents described herein as a separate composition. Methods of Use The present disclosure also provides methods for treating diseases or conditions in a subject in need thereof, the methods comprising administering to the subject a provided 11760147.1 composition. The present disclosure also provides methods for preventing diseases or conditions in a subject in need thereof, the methods comprising administering to the subject a provided composition. The present disclosure also provides methods for reducing the risk of developing a disease or condition in a subject in need thereof. In certain embodiments, the disclosed compositions can be used to treat a subject (e.g., a human) having a disease or condition that would benefit from administration of a therapeutic agent. In certain embodiments, the subject is administered an effective amount of any one or more disclosed compositions. In certain embodiments, the subject is administered a therapeutically effective amount of any one or more disclosed compositions. In certain embodiments, the subject is administered a prophylactically effective amount of any one or more disclosed compositions. In certain embodiments, the subject is an animal. In certain embodiments, the subject is a mammal. In certain embodiments, the subject is a human. In certain embodiments, the subject is a human aged 18 years or older. In certain embodiments, the subject is a human aged 12-18 years, exclusive. In certain embodiments, the subject is a human aged 2-12 years, inclusive. In certain embodiments, the subject is a human younger than 2 years. In certain embodiments, the subject is a non-human animal. In certain embodiments, the subject is a non-human mammal. In certain embodiments, the disease or condition being treated is one associated with a specific biological target. In certain embodiments, the target is a voltage-gated sodium channel. In certain embodiments, the target is a site-1 sodium channel. In certain embodiments, the disease or condition is pain. The quality of life of patients suffering from postoperative or even chronic pain is often diminished by the need for repeated administration of systemic analgesic medications (e.g., opioids), which give rise to potentially serious complications and clouding of the sensorium. Typically, repeated administration of systemic analgesic medications requires that patients be tethered to an external device, which can prolong hospitalization and even require that recipients be maintained as inpatients. Further, existing pain management options limit the ability of patients suffering from postoperative pain or chronic pain to adjust the timing, intensity and duration of anesthetic effect. Peripheral nerves are surrounded by the perineurium, which is composed of a basal membrane with a layer of perineurial cells and tight junctions limiting paracellular permeability. Delivery of analgesic drugs is often impeded by the perineurium. For example, tetrodotoxin 11760147.1 (TTX) is an attractive candidate in peripheral nerve anesthesia because of its reduced affinity for voltage dependent sodium channels of the peripheral nerve, but a poor affinity for the cardiac sodium channel isoform. It also does not cross the blood brain barrier. Voltage-gated sodium channels play important roles in nociceptive nerve conduction, but candidate anesthetics (e.g., specific antagonists of sodium channels) are often not effective in vivo because of lack of permeability of the perineurial barrier. Hence, high concentrations of anesthetics and multiple dosages are often required to achieve clinically effective and prolonged anesthesia. Although permeation enhancers have been used to increase the permeability of lipid barriers and, they can be associated with myotoxicity. There exists a need for systems for the delivery of local anesthetic that can provide repeated or prolonged analgesia on-demand, following a single administration. In certain embodiments, the methods for treating diseases or conditions comprise administering the composition such that the therapeutic agent is delivered to a biological target at a rate that is less than if the therapeutic agent were administered alone. In such embodiments, the therapeutic agent is delivered via sustained release. In certain embodiments, the administration is local such that the sustained release is a local sustained release (i.e., local administration for a local effect, e.g., subcutaneous administration). In certain embodiments, administration is systemic such that the sustained release is a systemic sustained release (i.e., systemic administration for a dispersed or system-wide effect, e.g., parenteral administration). In certain embodiments, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 168 hours after administration of the composition to the subject. In certain embodiments, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 144 hours after administration of the composition to the subject. In certain embodiments, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 120 hours after administration of the composition to the subject. In certain embodiments, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 96 hours after administration of the composition to the subject. In certain 11760147.1 embodiments, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 72 hours after administration of the composition to the subject. In certain embodiments, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 48 hours after administration of the composition to the subject. In certain embodiments, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 24 hours after administration of the composition to the subject. In certain embodiments, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 12 hours after administration of the composition to the subject. In certain embodiments, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 6 hours after administration of the composition to the subject. In certain embodiments, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 3 hours after administration of the composition to the subject. In certain embodiments, duration of a therapeutic effect is extended by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1,000%, or at least 10,000% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by at least 10% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by at least 20% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula 11760147.1 (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by at least 30% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by at least 40% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by at least 50% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by at least 60% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by at least 70% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by at least 80% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by at least 90% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by at least 100% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended 11760147.1 by least 200% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by least 300% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by least 400% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by least 500% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by least 600% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by least 700% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by least 800% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by least 900% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by least 1,000% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, 11760147.1 tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, duration of a therapeutic effect is extended by least 10,000% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. In certain embodiments, the therapeutic effect is nerve block and / or reduced pain. In certain embodiments, the therapeutic effect is nerve block or reduced pain. In certain embodiments, the therapeutic effect is nerve block and reduced pain. In certain embodiments, the therapeutic effect is nerve block. In certain embodiments, the therapeutic effect is reduced pain. In certain embodiments, the therapeutic effect is reduction of pain by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 99% compared to a baseline level of pain prior to administration. The present disclosure also provides uses of a provided composition in a method described herein. The present disclosure also provides uses of a provided pharmaceutical composition in a method described herein. The present disclosure also provides a provided composition for use in a method described herein. The present disclosure also provides a provided pharmaceutical composition for use in a method described herein. EQUIVALENTS AND SCOPE In the claims articles such as “a,” “an,” and “the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process. Furthermore, the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is 11760147.1 dependent on the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the invention, or aspects of the invention, is / are referred to as comprising particular elements and / or features, certain embodiments of the invention or aspects of the invention consist, or consist essentially of, such elements and / or features. For purposes of simplicity, those embodiments have not been specifically set forth in haec verba herein. It is also noted that the terms “comprising” and “containing” are intended to be open and permits the inclusion of additional elements or steps. Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub-range within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise. This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the invention can be excluded from any claim, for any reason, whether or not related to the existence of prior art. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present invention, as defined in the following claims. 11760147.1 EXAMPLES In order that the disclosure described herein may be more fully understood, the following examples are set forth. The examples described in this application are offered to illustrate the compounds, pharmaceutical compositions, and methods provided herein and are not to be construed in any way as limiting their scope. Preparation of methyl-branched liposomes To examine the hypothesis that branching methyl groups within lipid bilayers could enhance sustained drug release (FIG.1A), TTX-encapsulating liposomes were prepared with 4ME-PC (TTX@Lipo-ME) and without (TTX@Lipo). 1,2-diphytanoyl-sn-glycero-3-phosphocholine (4ME-PC) TTX@Lipo were prepared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3- phosphatidylglycerol (DSPG), and cholesterol at a molar ratio of 3:3:2:3. DOPC was used as in clinically used liposomes (like DepoDur) for local injection. DSPG was used because its negative charge can improve the encapsulation of positively charged TTX. In TTX@Lipo-ME (FIG.1B), the DPPC was replaced with 4ME PC, which has the same chain length as DPPC but 4 methyl groups on each hydrocarbon chain. Smaller particles have larger surface to volume ratio and will allow more rapid water penetration, which will result in an increased ‘‘burst release’’ and generally more rapid release kinetics. Thus, large liposomes were prepared via a thin film hydration followed by vigorous agitation and freezing-thawing. TTX@Lipo-ME were spherical by cryogenic electron microscopy (Cryo-EM) (FIG.1C), with a diameter of 920 ± 61 nm (FIG.1D). TTX@Lipo and TTX@Lipo-ME had similar size (FIG.1D) and negative zeta potential (FIG.1E). TTX@Lipo-ME displayed no size change after storage at 4 °C for 8 weeks, indicating good stability (FIG.6). The viscosity of different formulations, an important factor for injectability, was measured at a range of angular frequencies. Both TTX@Lipo and TTX@Lipo-ME showed similar viscosity (< 60 mPa·s) to TTX in PBS, indicating good injectability (FIG.7). 11760147.1 Effect of branched lipids on payload release in vitro To assess if Lipo-ME could provide sustained drug release, a hydrophilic fluorophore sulforhodamine B (SRho, FIG.2A) was loaded into methyl branched liposomes (SRho@Lipo- ME) by hydrating the lipid cake with 10 mg / mL SRho in phosphate buffered saline (PBS). Given the same SRho feed, the SRho loading in SRho@Lipo-ME was 10% higher than in SRho@Lipo (FIG.2B). In the release set-up, free SRho was completely released within 6 hours. 12.5% SRho was released in the first 24 hours from SRho@Lipo and 6.6% SRho from SRho@Lipo-ME (FIG.2C), showing that encapsulation of SRho into liposomes slowed its release and methyl-branched lipids slowed release compared to unmodified liposomes. Similar loading and release experiments were performed with tetrodotoxin (TTX, FIG. 2D), a hydrophilic anesthetic with lower molecular weight than SRho. Given the same TTX feed, TTX@Lipo-ME enabled 16.2% higher loading of TTX than TTX@Lipo (FIG.2E).24.0% TTX was released from TTX@Lipo in the first 24 hours, while only 14.4% TTX was released from TTX@Lipo-ME in the same period (FIG.2F) To further confirm the broad applicability of methyl branched liposomes in drug delivery, the release kinetics of bupivacaine hydrochloride were compared (Bup, FIG.2G), an amphiphilic amino-amide local anesthetic in current clinical use, from Bup@Lipo and Bup@Lipo-ME. As with SRho and TTX, incorporation of 4ME-PC increased the loading (FIG. 2H) and slowed the release of Bup (FIG.2I). 100 nm liposomes (FIGs.8A-8B) were prepared to evaluate the effect of branched methyl groups on the release of a representative payload, Sulforhodamine B (SRho). It was found that branched methyl groups within lipid bilayers of 100 nm liposomes also increased loading of SRho (FIG.8C). In 24 hours, 34.3% of SRho was released from 100 nm SRho@Lipo, while SRho@Lipo-ME released only 13.2% of SRho (FIG.8D). This further confirmed that methyl-branched lipids decreased the release of SRho compared to their unmodified counterparts. In vitro cytotoxicity Before neurobehavioral testing in vivo, the in vitro cytotoxicity of TTX formulations to muscle and nerve was evaluated in myoblast C2C1217 and pheochromocytoma PC1218 cell lines, which are used to assess myo- and neurotoxicity, respectively. Different TTX formulations 11760147.1 were directly added into the cell culture media in conventional cell culture wells. After 24 h of incubation with different TTX formulations (TTX, TTX@Lipo, and TTX@Lipo-ME), cell viabilities were assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium) (MTS) assays. As shown in FIGs.9A-9B, all groups in both cell types showed cell viabilities comparable to untreated cells, suggesting that neither TTX@Lipo or TTX@Lipo-ME caused cytotoxicity. Sciatic nerve blockade in vivo To assess the impact of incorporation of methyl-branched lipids into liposomes on drug release in vivo, rat models of peripheral nerve block were employed. Rats were injected at the left sciatic nerve with 300 μL of different TTX formulations. Local anesthesia was assessed with a modified hotplate test where thermal latency, the time in seconds a rat left its hindpaws on a hotplate, was measured in both hindpaws (2 seconds was the baseline, and 12 seconds was maximal). A sensory block was considered successful if the latency was longer than 7 seconds (the midpoint between baseline and maximum latency). The duration of sensory nerve block was defined as the time for thermal latency to return to 7 seconds. The duration of deficits in the injected (left) hindpaw reflected the duration of sensory nerve block, whereas deficits in the contralateral uninjected (right) hindpaw indicated effects from systemic distribution of TTX (i.e., systemic toxicity). TTX doses were selected based on a previous report, where 4-5 μg of TTX produced 1.5 – 2.5 h of sciatic nerve block. The duration of blocks in the injected and contralateral sides increased with increasing doses of TTX.4 μg of TTX at the sciatic nerve resulted in a mean duration of sensory nerve block of 2.2 ± 0.4 h (FIG.3A), with contralateral block lasting 2.0 ± 0.4 h. That dose of free TTX induced 100% contralateral blocks (FIG.3B).5 μg of TTX was uniformly fatal (FIG.3C). The starting dose of TTX in liposomes was adapted from previous work, where 15.8 μg of TTX in liposomes produced effective sciatic nerve blockade lasting 13.5 hours. Here, TTX@Lipo containing 15 μg TTX provided sensory nerve blockade lasting 11.2 ± 1.9 h, while nerve block from the same dose of TTX in TTX@Lipo-ME lasted 21.9 ± 3.1 h (FIG.3A). TTX@Lipo-ME provided longer blocks than TTX@Lipo for the same dose of TTX at every dose of TTX tested (FIG.3A). TTX@Lipo-ME containing 25 μg TTX prolonged the duration of nerve block to 48.2 ± 5.4 h. The same dose of TTX in TTX@Lipo was fatal (FIG.3C). 11760147.1 Dose-dependent contralateral block was observed with TTX, free or in liposomes (FIG.3B). With TTX@Lipo-ME, contralateral latency became elevated at higher doses of TTX than with TTX@Lipo. Contralateral block was seen in 3 of 4 tested rats when TTX dose was increased to 25 µg, a dose that was fatal with TTX@Lipo. In all animals, motor nerve block was assessed by a weight-bearing test. There was no statistically significant difference between the durations of sensory and motor nerve block (P > 0.05), even though the mean durations of motor block were longer than those of sensory block for the liposomal formulations (FIG.10). These data were consistent with the slower release kinetics from methyl-branched liposomes (i.e., liposomes comprising the lipid of Formula (I)) and demonstrated that branched liposomes resulted in prolonged block and reduced systemic toxicity. Optimization of the liposomal formulation to enhance nerve blockade The effect of the molar percentage of branched lipids on the duration of nerve block, at a constant TTX dose of 25 µg (FIG.3D) was investigated. Formulations with 10%, 27%, and 50% branched lipids provided nerve block lasting 42.8 ± 5.0 h, 50.2 ± 5.8 h, and 69.6 ± 7.2 h, respectively. Further increasing the molar percentage of branched lipids to 100% did not further increase or decrease the duration of nerve blocks. Localization and retention of liposomal formulations To assess the local retention of formulations, liposomes were covalently conjugated with Cy5.5 and injected at the sciatic nerve. The fluorescent intensity at the injection site was recorded at predetermined intervals with an in vivo imaging system (IVIS) (FIG.4A). Free Cy5.5 was completely cleared after 1 day. Both unmodified liposomes (Cy5.5-Lipo) and methyl- branched liposomes (Cy5.5-Lipo-ME) remained at the injection site for at least 3 weeks (FIG. 4B). These results suggested that liposomes with or without methyl-branched lipids have similar local retention times and differences in in vivo nerve block duration between unmodified and methyl-branched liposomes would be due to differences in drug release. Tissue reaction Local anesthetics, especially prolonged duration local anesthetics, can be associated with myotoxicity and inflammation, although this is generally not the case with site 1 sodium channel 11760147.1 blockers such as TTX. Drug carriers themselves can also cause inflammation or myotoxicity that outlasts the duration of nerve block.4 and 14 days after injection, the sciatic nerves and surrounding tissues were harvested and sectioned, and tissue reaction was assessed by hematoxylin and eosin (H&E) staining. All slides were scored for inflammation (0–4) and myotoxicity (0–6; see Methods). Histological images from untreated rats are in FIG.11. Inflammation in rats injected with TTX@Lipo-ME on day 4 (score = 1 or 2 in all animals) was minimal to mild and was diminished by day 14 (score = 1 in all animals; P = 0.035; Table S1). There was no statistically significant difference in inflammation scores between TTX@Lipo and TTX@Lipo-ME at either time point (P > 0.05). Inflammation was largely restricted to muscle fascicles with very minimal intramuscular extension (FIG.5A and FIG.12) which is also commonly seen with drug delivery vehicles. Minimal myotoxicity (score = 0 or 1 in all animals, Table 2) was observed in some rats injected with liposomes (FIG.5A). Sciatic nerves were stained with toluidine blue due to the low sensitivity of H&E staining for nerve damage. In all formulations tested, no nerve injury was seen at either time point (FIG.5B and FIG.13). Discussion Here, the performance of a liposomal depot drug delivery system was greatly improved by incorporating methyl-branched lipid (4ME-PC) into the lipid bilayers, mimicking a feature of archaeal membrane. Lipo-ME increased the drug loading and decreased the release of different payloads. Incorporation of 4ME-PC in ~1 µm liposomes (TTX@Lipo-ME) prolonged the duration of local anesthesia from TTX in vivo from 16 hours to 70 hours and reduced systemic toxicity. Since incorporation of methyl-branched lipids also increased loading and slowed release from 100 nm liposomes, it is likely that systemically administered liposomes would also benefit from such modification. The passive diffusion of molecules through lipid bilayers is the rate-limiting step in the transportation across both cellular and artificial membranes, such as those in liposomes. The presence of branching methyl groups in Archaeal lipids make the membrane structure more tightly packed and less permeable to small molecules compared to bacterial and eukaryotic membranes. The current study demonstrated that the methyl branched lipids inspired by Archaea lipids can enhance lipid membrane-based drug delivery systems. 11760147.1 Tissue reaction to TTX@Lipo-ME injected at the rat sciatic nerve was benign at the doses tested. On histological sections 4 days after injection, only minimal to mild inflammation (score = 1 or 2) was observed. For the purpose of comparison, it has been shown that inflammation scores in rats treated with 0.5% (w / v) bupivacaine HCl and Exparel (a commercially available liposomal bupivacaine formulation) were higher in the same animal model. TTX@Lipo-ME induced minimal myotoxicity (score = 0 or 1 in all animals, Table 2), lower than for 0.5% (w / v) bupivacaine HCl and Exparel. These results suggest that inflammation and myotoxicity were lesser in TTX@Lipo-ME than clinically used concentrations of bupivacaine and Exparel. Therefore, biocompatibility and safety are unlikely to be obstacles to the potential translation of Lipo-ME. Unlike most liposome studies, the clinical application model used here involved local effect following local administration. Neurobehavior testing serves as a bioassay for assessing local and systemic drug distribution. In this context, the neurobehavioral deficits in the injected extremity are a relevant bioassay for examining local drug kinetics. Similarly, neurobehavioral deficits in the contralateral (uninjected) extremity present a reliable bioassay for assessing systemic drug distribution. In this case, it provides insights into the presence of TTX in the bloodstream. The reduced contralateral block and mortality as shown in FIGs.3A-3D clearly demonstrated that incorporating methyl-branched lipids affected the systemic pharmacokinetics of TTX, reducing biotoxicity and allowing larger doses and longer durations of effect. Pain is one of the most common medical conditions associated with many diseases. Unfortunately, current pain management relies heavily on opioids, which may lead to severe side effects including nausea, pruritus, addiction, and overdose. Drug delivery technologies have emerged as promising approaches to prolonging the duration of local anesthesia, which requires a therapeutic level of drugs at the nerve sites over an extended period. Herein is described a formulation that provides three days of nerve block following a single injection. The compositions disclosed herein incorporating methyl-branched liposomes (i.e., having a lipid of Formula (I)) increased the drug loading and reduced the release of encapsulated compounds compared to unmodified liposomes. In vivo, they greatly prolonged the duration of local anesthesia from TTX, a small hydrophilic and charged molecule, and mitigated systemic toxicity. Experimental Methods 11760147.1 Chemicals and Materials 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-diphytanoyl-sn-glycero-3- phosphocholine (4-ME PC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl- sn-glycero-3-phospho-(1'-rac-glycerol) (DSPG), and Cy5.5-DOPC were purchased from Avanti Polar Lipids (Alabaster, AL, USA). Sulforhodamine B, cholesterol, chloroform, tert-butanol, octyl-β-D-glucopyranoside were purchased from Sigma-Aldrich (St. Louis, MO, USA). Tetrodotoxin (TTX) was obtained from Cayman Chemical Company (Ann Arbor, Michigan, USA). TTX ELISA kits were purchased from Reagen LLC (Moorestown, NJ, USA). Dulbecco’s phosphate buffered saline (PBS) were purchased from Thermo Fisher Scientific (Waltham, MA, USA). Scheme 1 depicts routes for the preparation of alkyl-branched phospholipids such as lipid (1) (a) and aromatic group-branched phospholipids (b). Liposome preparation and characterization The liposomes were prepared using the thin-film hydration method followed by agitation and freeze-thaw method1. In brief, the lipid formulation (4ME PC, DOPC, DSPG and cholesterol at a molar ratio of 3:3:2:3 was dissolved in a solution of chloroform and methanol (ratio: 9:1). The solvent was evaporated under reduced pressure, and the lipid was redissolved in tert-butanol, followed by freeze-drying. The lipid cake was hydrated with SRho, TTX in PBS buffer (pH=7.4) or hydrated with bupivacaine hydrochloride in saline. After ten freeze-thaw 11760147.1 cycles, the solution was dialyzed against PBS or water for 48 h in a dialysis tube with a molecular mass cut-off of 1,000 kDa (Spectra / Por™ Float-A-Lyzer™ G2 Dialysis Devices). The dialysis media were changed with fresh PBS or saline at least twice a day. Drugs and dye in all formulations were quantitated after disruption of the liposome with octyl-β-D-glucopyranoside (100 mM, volume ratio of 2:1 to formulations). Instruments and characterization of materials Dynamic light scattering (DLS) (Zetasizer Pro; Malvern Panalytical, USA) was used to determine the hydrodynamic diameter and zeta potential of liposomes. An Agilent 1260 series high-performance liquid chromatography (HPLC) with a UV-vis detector was used for analyzing the Bupivacaine hydrochloride in the releasing experiments. Viscosity was tested on a TA DHR-2 rheometer with a frequency of 1 Hz, shear strain of 1%, and a temperature of 25 °C. Cryo-EM imaging Quantifoil copper EM grids (R2 / 1, 400 mesh) were glow-discharged for 30 seconds at 15mA. This grid was loaded into the Vitrobot climate chamber at 100% humidity.10 mg / mL samples of methyl-branched and non-methyl-branched liposome samples were prepared and 5 μL aliquots were manually dispensed onto the grids. Grids were blotted for 5 seconds with a wait time of 5 seconds and then plunged into liquid ethane for vitrification. Frozen grids were stored in liquid nitrogen until use. Cryo-EM grids were imaged on a Titan Krios II equipped with a Gatan K3 camera at 1.4 Å / pixel. Image analysis and scaling were then done through ImageJ. Cell culture Cell culture of C2C12 mouse myoblasts (American Type Culture Collection (ATCC), Manassas, VA, USA) and PC12 rat adrenal gland pheochromocytoma cells (ATCC, Manassas, VA, USA) were performed. In brief, C2C12 cells were cultured in DMEM with 20% FBS and 1% Penicillin Streptomycin. Cells were seeded onto a 24-well plate at 50,000 cells / mL and incubated for 10–14 days in DMEM with 2% horse serum and 1% Penicillin Streptomycin to differentiate into myotubules. PC12 cells were grown in DMEM with 12.5% horse serum, 2.5% FBS, and 1% Penicillin Streptomycin. Cells were seeded onto a 24-well-plate, and 50 ng / mL nerve growth factor was added 24 h after seeding. 11760147.1 Cell Viability To determine cytotoxicity, different formulations were directly added into the cell culture media and incubated in the media bathing the cells (i.e., in direct contact with them) in conventional cell culture wells (lipid concentration: 20 mg / mL). After 24 hours, cell viabilities were evaluated with the MTS assay, and their survival was expressed as percentages of results in untreated cells. In vitro drug release Cumulative release of small molecules (Sulforhodamine B, Tetrodotoxin, Bupivacaine hydrochloride) were performed by placing 200 μL of samples into a Slide-A-Lyzer MINI dialysis device (Thermo Fisher Scientific, Waltham, MA) with a 10,000 MW cut-off, further dialyzed with 14 mL release media and incubated at 37 °C on a platform shaker (New Brunswick Innova 40, 60 rpm). At predetermined intervals, the dialysis solution was exchanged with fresh, pre-warmed release media. The release media of Sulforhodamine B, Tetrodotoxin was PBS (pH=7.4). The release media of Bupivacaine hydrochloride was physiological saline. The concentration of TTX in release media was quantified by an enzyme-linked immunosorbent assay (ELISA, Reagen LLC). The concentration of Sulforhodamine B in release media was determined by a plate reader (BioTek, Winooski, VT) with excitation and emission wavelengths of 560 nm and 580 nm. The concentration of bupivacaine hydrochloride (Bup) in release media was determined by high-performance liquid chromatography. The concentrations of SRho, TTX and Bup in release studies were 4 mM, 0.3 mM and 20 mM. Animal studies Animal studies were conducted following protocols approved by the Boston Children’s Hospital Animal Care and Use Committee in accordance with the guidelines of the International Association for the Study of Pain. Adult male Sprague–Dawley rats (Charles River Laboratories, Wilmington, MA, USA) weighing 400–450 g were housed in groups under a 12-h / 12-h light / dark cycle with lights on at 6:00 AM. Sciatic nerve injections were performed with a 23 G needle at the left sciatic nerve under brief isoflurane-oxygen anesthesia. The needle was introduced posteromedial to the greater trochanter, pointing in an anteromedial direction, and upon contact with bone, the formulations 11760147.1 were injected onto the sciatic nerve. Neurobehavioral testing was done on both hindquarters. Deficits in the right (uninjected) extremity served as a metric of systemic drug distribution. Sensory nerve blockade was assessed by modified hotplate testing. In brief, hind paws were exposed in sequence (left then right) to a 56 °C hot plate (Stoelting, Wood Dale, IL, USA), and the time the animal allowed its paw to remain on the hotplate (thermal latency) was measured. A thermal latency of 2 seconds indicated no nerve blockade (baseline), and a thermal latency of 12 seconds was maximal latency. Successful nerve blockade was defined as achieving a thermal latency above 7 seconds. Hind paws were removed from the hotplate after 12 seconds to prevent thermal injury. Measurements were repeated three times in each animal at each time point and the mean was used for further data analysis. Motor nerve block was assessed by a weight-bearing test to determine the motor strength of the rat’s hind paw. In brief, the rat was positioned with one hind paw on a digital balance and was allowed to bear its own weight. The maximum weight that the rat could bear without the ankle touching the balance was recorded, and motor block was considered achieved when the motor strength was less than half-maximal. Measurements were repeated three times at each time point and the mean was used for further data analysis. Duration of sensory block was calculated as the time required for thermal latency to return to 7 seconds (halfway between the baseline and maximal latencies). The duration of motor block was defined as the time it took for the weight-bearing to return to halfway between normal and maximal block. In vivo imaging system (IVIS) imaging Cy5.5-conjugated DOPC was used in the preparation of Cy5.5-labeled liposomes following the same procedures as described previously with Cy5.5 molar concentration at 0.2 mg / mL. Under isoflurane-oxygen anesthesia, rats were shaved and injected with 0.3 mL of different Cy5.5-labeled liposomal formulations. The in vivo fluorescence images were captured, and the fluorescence intensity was evaluated at predetermined time points post-injection (under brief isoflurane-oxygen anesthesia) using a Spectrum IVIS (PerkinElmer, MA, USA). Whole- body animal images were recorded non-invasively. The 745 nm excitation filter and the 800 nm emission filter were used for the imaging. Quantitative analysis was carried out using the Live Imaging® software of the IVIS. 11760147.1 Tissue harvesting and histology Rats were sacrificed at 4 and 14 days after the injection (as it has been found that these time points are useful in evaluating both acute and chronic inflammation and myotoxicity), and the sciatic nerve was harvested together with surrounding tissues. The samples were scored for inflammation (0–4) and myotoxicity (0–6). All scoring and other histological assessments were performed by an observer blinded as to the nature of the individual samples. The inflammation score was a subjective quantification of severity in which 0 was normal and 4 was severe inflammation. The myotoxicity score was determined by the nuclear internalization and regeneration of myocytes, two representative characteristics of local anesthetics’ myotoxicity. Nuclear internalization was characterized by myocytes having nuclei located away from their usual location at the periphery of the cell. Regeneration was characterized by the presence of shrunken myocytes with basophilic cytoplasm. The scoring scale was as follows: 0 = normal; 1 = perifascicular internalization; 2 = deep internalization (more than five cell layers); 3 = perifascicular regeneration; 4 = deep tissue regeneration (more than five cell layers); 5 = hemifascicular regeneration; 6 = holofascicular regeneration. To evaluate the neurotoxicity of formulations, the sciatic nerves were fixed in Karnovsky’s KII solution, processed and Epon-embedded for toluidine blue staining. They were assessed by optical microscopy in a masked fashion. Statistical Analysis Statistical comparisons were performed using the unpaired two-tailed t-test unless stated otherwise. Thermal latency, inflammation and myotoxicity scores were reported as means and quartiles due to their ordinal or non-Gaussian character. Data are presented as means ± SD (n = 4) in release kinetics, cell work, neurobehavioral, and histology studies. Data were considered statistically significant if P < 0.05 (***P < 0.001, **P < 0.01, *P < 0.05). Table 1: Inflammation 4 and 14 days after injection of formulations. 11760147.1 Inflammation scores: 0–4. P values result from the comparison of liposomal formulations to the untreated group (Mann Whitney U test). There were no statistically significant differences between liposomal formulations. Data are medians with 25th and 75th percentiles in parentheses; n = 4. Table 2: Myotoxicity 4 and 14 days after injection of formulations. Myotoxicity scores: 0–6. P values result from the comparison of liposomal formulations to the untreated group (Mann Whitney U test). There was no statistically significant difference in myotoxicity scores between different liposome groups and the untreated groups. Data are medians with 25th and 75th percentiles in parentheses; n = 4. 11760147.1

Claims

CLAIMS What is claimed is:

1. A composition comprising a liposome encapsulating a therapeutic agent or a diagnostic agent, wherein the liposome comprises a lipid of Formula (I):or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, wherein: m is an integer of 0-12; n is an integer of 0-12; x is an integer of 0-6; y is an integer of 0-6; R1is a phosphoglycerol, phosphocholine, phosphoethanolamine, phosphoinositol, or phosphoserine moiety; each R2is independently hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, -ORD1, -N(RD1a)2, -SRD1, -SO2, -NO2, -N3, or -CN, wherein at least one instance of R2is not hydrogen; each R3is independently hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, -ORD1, -N(RD1a)2, -SRD1, -SO2, -NO2, -N3, or -CN, wherein at least one instance of R3is not hydrogen; X1is substituted or unsubstituted C1-6alkylene; X2is substituted or unsubstituted C1-6 alkylene; wherein each RD1is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted cycloalkynyl group, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom; and 11760147.1wherein each RD1ais independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted linear alkynyl, optionally substituted cycloalkynyl group, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or a nitrogen protecting group; or optionally two instances of RD1aare taken together with their intervening atoms to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring.

2. The composition of claim 1, wherein the liposome further comprises an anionic phospholipid.

3. The composition of claim 2, wherein the liposome comprises about 1-25 mol% of the anionic phospholipid.

4. The composition of claim 2 or 3, wherein the liposome comprises about 15-20 mol% of the anionic phospholipid.

5. The composition of any of claims 2-4, wherein the liposome comprises about 18 mol% of the anionic phospholipid.

6. The composition of any of claims 2-5, wherein the anionic phospholipid is a phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidic acid (PA), diphosphatidylglycerol (DPG) or cardiolipin (CL), or a derivative or mixture thereof 7. The composition of any of claims 2-6, wherein the anionic phospholipid is 1,2- distearoyl-sn-glycero-3-phosphatidylglycerol (DSPG), 1,2-dipalmitoyl-sn-glycero-3- phosphoglycerol (DPPG), 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG), 1,2- dilauroyl-sn-glycero-3-phospho-L-serine (DSPS), 1,2-dipalmitoyl-sn-glycero-3-phospho-L- serine (DPPS), 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS), 1,2-distearoyl-sn- glycero-3-phosphate (DSPA), 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA), or 1,2- dimyristoyl-sn-glycero-3-phosphate (DMPA), or mixture thereof. 11760147.

18. The composition of any of claims 2-7, wherein the anionic phospholipid is 1,2- distearoyl-sn-glycero-3-phosphatidylglycerol (DSPG).

9. The composition of any of claims 1-8, wherein the liposome further comprises a zwitterionic phospholipid.

10. The composition of claim 9, wherein the liposome comprises about 1-50 mol% of the zwitterionic phospholipid.

11. The composition of claim 9 or 10, wherein the liposome comprises about 1-30 mol% of the zwitterionic phospholipid.

12. The composition of any of claims 9-11, wherein the liposome comprises about 5 mol%, about 25 mol%, about 27 mol%, or about 45 mol% of the zwitterionic phospholipid.

13. The composition of any of claims 9-12, wherein the zwitterionic phospholipid is a phosphatidylethanolamine (PE) or a phosphatidylcholine (PC), or a derivative or mixture thereof.

14. The composition of any of claims 9-13, wherein the zwitterionic phospholipid is 1,2- dioleoyl-sn-glycero-3-phospho-choline (DOPC), 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE), 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine, or 1,2- dipalmitoleoyl-sn-glycero-3-phosphoethanolamine, or mixture thereof.

15. The composition of any of claims 9-14, wherein the zwitterionic phospholipid is 1,2- dioleoyl-sn-glycero-3-phospho-choline (DOPC).

16. The composition of any of claims 1-15, wherein the liposome further comprises a sterol.

17. The composition of claim 16, wherein the liposome comprises about 1-35 mol% of the sterol. 11760147.

118. The composition of claim 16 or 17, wherein the liposome comprises about 25-30 mol% of the sterol.

19. The composition of any of claims 16-18, wherein the liposome comprises about 27 mol% of the sterol.

20. The composition of any of claims 16-19, wherein the sterol is cholesterol, a cholesteryl ester, vitamin D, or a phytosterol, or a derivative or mixture thereof.

21. The composition of any of claims 16-20, wherein the sterol is cholesterol, desmosterol, lanosterol, zymosterol, ergosterol, stigmasterol, or campestanol.

22. The composition of any of claims 16-21, wherein the sterol is cholesterol.

23. The composition of any of the preceding claims, wherein the liposome comprises about 5-97 mol% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof.

24. The composition of any of the preceding claims, wherein the liposome comprises about 25-50 mol% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof.

25. The composition of any of the preceding claims, wherein the liposome comprises about 10 mol%, about 27 mol%, about 30 mol%, about 50 mol%, or about 100 mol% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof.

26. The composition of any of the preceding claims, wherein the liposome comprises: (i) an anionic phospholipid; (ii) a zwitterionic phospholipid; (iii) a sterol; and (iv) the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. 11760147.

127. The composition of claim 26, wherein the liposome comprises: (i) about 1-25 mol% of the anionic phospholipid; (ii) about 1-50 mol% of the zwitterionic phospholipid; (iii) about 1-35 mol% of the sterol; and (iv) about 5-97 mol% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof.

28. The composition of claim 26 or 27, wherein the liposome comprises: (i) about 18 mol% of the anionic phospholipid; (ii) about 27 mol% of the zwitterionic phospholipid; (iii) about 27 mol% of the sterol; and (iv) about 27 mol% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof; (i) about 18 mol% of the anionic phospholipid; (ii) about 25 mol% of the zwitterionic phospholipid; (iii) about 27 mol% of the sterol; and (iv) about 30 mol% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof; (i) about 18 mol% of the anionic phospholipid; (ii) about 5 mol% of the zwitterionic phospholipid; (iii) about 27 mol% of the sterol; and (iv) about 50 mol% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof; (i) about 18 mol% of the anionic phospholipid; (ii) about 45 mol% of the zwitterionic phospholipid; (iii) about 27 mol% of the sterol; and (iv) about 10 mol% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof; or about 100 mol% of the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof.

29. The composition of any of the preceding claims, wherein R1is an unsubstituted phosphoglycerol, unsubstituted phosphocholine, unsubstituted phosphoethanolamine, unsubstituted phosphoinositol, or unsubstituted phosphoserine moiety.

30. The composition of any of the preceding claims, wherein R1is an unsubstituted phosphocholine moiety. 11760147.

131. The composition of any of the preceding claims, wherein X1is unsubstituted C1-4 alkylene.

32. The composition of any of the preceding claims, wherein X1is unsubstituted propylene.

33. The composition of any of the preceding claims, wherein X2is unsubstituted C1-4alkylene.

34. The composition of any of the preceding claims, wherein X2is unsubstituted propylene.

35. The composition of any of the preceding claims, wherein m is 0 or 1.

36. The composition of any of the preceding claims, wherein m is 1.

37. The composition of any of the preceding claims, wherein n is 0 or 1.

38. The composition of any of the preceding claims, wherein n is 1.

39. The composition of any of the preceding claims, wherein x is 0-3.

40. The composition of any of the preceding claims, wherein x is 3.

41. The composition of any of the preceding claims, wherein y is 0-3.

42. The composition of any of the preceding claims, wherein y is 3.

43. The composition of any of the preceding claims, wherein each R2is independently hydrogen, optionally substituted alkyl, or optionally substituted aryl, wherein at least one instance of R2is not hydrogen. 11760147.

144. The composition of any of the preceding claims, wherein each R2is independently hydrogen, methyl, -CH2OPh, ethyl, or unsubstituted phenyl, wherein at least one instance of R2is not hydrogen.

45. The composition of any of the preceding claims, wherein each R2is independently optionally substituted alkyl or optionally substituted aryl.

46. The composition of any of the preceding claims, wherein each R2is independently methyl, ethyl, or phenyl.

47. The composition of any of the preceding claims, wherein each R3is independently hydrogen, optionally substituted alkyl, or optionally substituted aryl, wherein at least one instance of R3is not hydrogen.

48. The composition of any of the preceding claims, wherein each R3is independently hydrogen, methyl, -CH2OPh, ethyl, or unsubstituted phenyl, wherein at least one instance of R3is not hydrogen.

49. The composition of any of the preceding claims, wherein each R3is independently optionally substituted alkyl or optionally substituted aryl.

50. The composition of any of the preceding claims, wherein each R3is independently methyl, ethyl, or phenyl.

51. The composition of any of the preceding claims, wherein the lipid of Formula (I) is of Formula (I-a):or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof. 11760147.

152. The composition of any of the preceding claims, wherein the lipid of Formula (I) is of Formula (I-a-1):or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof.

53. The composition of any of the preceding claims, wherein the lipid of Formula (I) is of Formula (I-a-2):or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof.

54. The composition of any of the preceding claims, wherein the lipid of Formula (I) is of Formula (I-b):or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, wherein: p is an integer of 8-20; and q is an integer of 8-20.

55. The composition of any of the preceding claims, wherein the lipid of Formula (I) is of Formula (I-b-1): 11760147.1or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof, wherein: p is an integer of 8-20; and q is an integer of 8-20.

56. The composition of any of the preceding claims, wherein the lipid of Formula (I) is of Formula (I-b-2):or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof.

57. The composition of any of the preceding claims, wherein the lipid of Formula (I) is of11760147.1or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof.

58. The composition of any of the preceding claims, wherein the liposome encapsulates a therapeutic agent.

59. The composition of any of the preceding claims, wherein the liposome encapsulates a diagnostic agent.

60. The composition of any of the preceding claims, wherein the therapeutic agent is a small molecule.

61. The composition of any of the preceding claims, wherein the therapeutic agent is an anesthetic. 11760147.

162. The composition of any of the preceding claims, wherein the therapeutic agent is a site 1 sodium channel blocker, amino ester anesthetic, or an amino amide anesthetic, or a derivative thereof.

63. The composition of any of the preceding claims, wherein the therapeutic agent is tetrodotoxin, saxitoxin, neosaxitoxin, bupivacaine, amylocaine, ambucaine, articaine, benzocaine, benzonatate, butacaine, butanilicaine, carbocaine, cepastat, chloraseptic, chloroprocaine, cinchocaine, citanest, cyclomethycaine, dibucaine, diperodon, dimethocaine, eucaine, etidocaine, fomocaine, fotocaine, hydroxyprocaine, isobucaine, levobupivacaine, lidocaine, marcaine, mepivacaine, meprylcaine, metabutoxycaine, nitracaine, orthocaine, orabloc, oxetacaine, oxybuprocaine, paraethoxycaine, phenacaine, piperocaine, piridocaine, polocaine, posimir, pramocaine, prilocaine, primacaine, procaine, procainamide, proparacaine, propoxycaine, pyrrocaine, quinisocaine, ropivacaine, sensorcaine, septocaine, trimecaine, tetracaine, tolycaine, tropacocaine, ulcerease, xylocaine, zorcaine, decarbamoyl saxitoxin, gonyautoxins, or derivatives thereof.

64. The composition of any of the preceding claims, wherein the therapeutic agent is tetrodotoxin or bupivacaine.

65. The composition of any of the preceding claims, further comprising a pharmaceutically acceptable excipient.

66. The composition of any of the preceding claims, wherein the composition is characterized in that, when tested in vitro by placing the composition in a medium, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 24 hours after placing the composition in the medium.

67. The composition of any of the preceding claims, wherein the composition is characterized in that, when administered to a subject, less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, 11760147.1or less than 10% of the therapeutic agent is released from the composition 24 hours after administration of the composition.

68. The composition of any of the preceding claims, wherein the composition is characterized in that, when administered to a subject, duration of a therapeutic effect is extended by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, or at least 200% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof.

69. The composition of claim 68, wherein the therapeutic effect is nerve block and / or reduced pain.

70. A method of treating a disease or condition, the method comprising administering an effective amount of the composition of any of the preceding claims to a subject in need thereof.

71. The method of claim 70, wherein less than 100%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% of the therapeutic agent is released from the composition 24 hours after administration of the composition to the subject.

72. The method of claim 70 or 71, wherein duration of a therapeutic effect is extended by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 200%, at least 300%, at least 400%, at least 500%, at least 600%, at least 700%, at least 800%, at least 900%, at least 1,000%, or at least 10,000% compared to duration of a therapeutic effect upon administration of the therapeutic agent alone or in a composition without the lipid of Formula (I), or a salt, co-crystal, tautomer, stereoisomer, solvate, hydrate, polymorph, or an isotopically enriched derivative thereof.

73. The method of claim 72, wherein the therapeutic effect is nerve block and / or reduced pain. 11760147.

174. The method of any of claims 70-73, wherein the disease or condition is pain.

75. The method of any of claims 70-74, wherein the subject is a mammal.

76. The method of any of claims 70-75, wherein the subject is a human.

77. A kit comprising the composition of any of the preceding claims and instructions for use. 11760147.1

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