Compositions and methods for delivery of therapeutic peptides
Patent Information
- Authority / Receiving Office
- EP · EP
- Patent Type
- Applications
- Current Assignee / Owner
- THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
- Filing Date
- 2024-07-23
- Publication Date
- 2026-06-03
AI Technical Summary
Current insulin treatments for Type 2 diabetes are burdensome, leading to poor patient compliance and risk of hypoglycemic events, while incretin mimetic treatments require daily or weekly injections and have stability and administration challenges.
Development of dynamic hydrogel compositions that encapsulate therapeutic peptides like incretin mimetics, utilizing polymer nanoparticle hydrogels with shear-thinning and self-healing properties for sustained, controlled release of therapeutic peptides.
The dynamic hydrogel system provides a tunable platform for prolonged delivery of therapeutic peptides, reducing the frequency of administration, improving patient compliance, and maintaining consistent drug release, thus avoiding side effects and enhancing therapeutic efficacy.
Smart Images

Figure US2024039172_30012025_PF_FP_ABST
Abstract
Description
[0001]Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO COMPOSITIONS AND METHODS FOR DELIVERY OF THERAPEUTIC PEPTIDES CROSS REFERENCE TO RELATED APPLICATION(S) The present application claims the benefit of priority to U.S. Provisional Application No. 63 / 528,525, filed July 24, 2023, and U.S. Provisional Application No. 63 / 569,651, filed March 25, 2024, the disclosures of each of which are incorporated by reference herein in their entirety. INCORPORATION BY REFERENCE OF SEQUENCE LISTING The present application contains an electronic Sequence Listing in XML file format named “APL_010WO_SL.xml,” created on July 9, 2024, and having a size of 2,650 bytes, the contents of which are incorporated by reference herein in its entirety. TECHNICAL FIELD The present technology generally relates to drug delivery, and in particular, to compositions and methods for delivery of therapeutic peptides. BACKGROUND Diabetes or pre-diabetes affects approximately 500 million people worldwide, including an estimated 130 million individuals in the U.S. In the U.S. alone, the annual spendings directly related to diabetes and pre-diabetes amounts to roughly $400 billion, making it the tenth most costly disease in the U.S. Type 2 diabetes (T2D), which accounts for 90–95% of all diabetes cases, is a metabolic disorder characterized by insulin resistance, deterioration of pancreatic ȕ-cell function, and impaired regulation of hepatic glucose production eventually leading to ȕ-cell failure. Patients with poorly managed T2D are at risk of serious micro- and macrovascular complications, including cardiovascular disease, nephropathy, retinopathy, neuropathy, and stroke. Current insulin treatments for T2D are highly burdensome, resulting in poor patient compliance, and can sometimes cause dangerous hypoglycemic events. In contrast, Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO treatment strategies based on incretin mimetics, which mimic natural incretin hormones that are secreted following carbohydrate intake, eliminate the risk of hypoglycemia. These treatments lower endogenous glucose production and drive expansion of insulin-secreting ȕ- cells to restore the native ability of patients to regulate glycemia. However, conventional treatments with incretin mimetics involve daily or weekly injections, which is a significant patient burden and results in poor compliance. BRIEF DESCRIPTION OF THE DRAWINGS Many aspects of the present disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale. Instead, emphasis is placed on illustrating clearly the principles of the present disclosure. FIGS. 1A and 1B illustrate PNP hydrogels for the prolonged delivery of therapeutic peptides. FIG. 1A is a schematic illustration of a polymer nanoparticle (PNP) hydrogel prepared by mixing of hydrophobically-modified hydroxypropylmethylcellulose (HPMC) with poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) nanoparticles that allows for facile encapsulation of a therapeutic peptide. FIG. 1B is a schematic illustration of formation of a localized depot in the subcutaneous space following subcutaneous injection of the PNP hydrogel which can provide a tunable platform for sustained release of a therapeutic peptide. FIG. 2A is a graph indicating that once weekly dosing frequency does not significantly improve patient compliance compared to a once daily dosing frequency. FIG. 2B is a graph of clinical data showing the release profile of conventional incretin mimetic treatments, where the dotted line in the bottom graph represents repeated weekly injections that patients take every week for four months to reach therapeutic concentrations of the incretin mimetic. Conventional treatment strategies involve daily or weekly subcutaneous injections with significant ramp-up time to achieve therapeutic concentrations. In contrast, the solid line in the top graph represents the target delivery profile of a single PNP hydrogel depot injection that sustains release of the incretin mimetic for 120 days. The dashed line in both graphs indicates the therapeutic threshold. FIG.3A is a graph showing a size exclusion chromatogram (SEC) trace of PEG- PLA polymer. Gel permeation chromatography characterization of the PEG-PLA polymer Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO showed a single peak corresponding to the PEG-PLA block co-polymer (Mn = 22 kDa; Ð = 1.08). FIG. 3B is a graph showing dynamic light scattering (DLS) data of PEG-PLA nanoparticles after nanoprecipitation (DH = 33.2, PDI = 0.038). FIG.4 shows a series of photographs illustrating preparation of PNP hydrogels. PNP hydrogels were prepared by mixing a solution of hydrophobically-modified HPMC (“polymer solution,” right syringe) with a solution of PEG-PLA nanoparticles and therapeutic peptide (e.g., semaglutide) (“NP solution,” left syringe) using a Luer lock mixer. After mixing, a homogenous, bubble-free, solid-like PNP hydrogel was formed. Owing to their dynamic crosslinking, PNP hydrogels are injectable through clinically relevant, high gauge needles and rapidly self-heal after injection. FIGS.5A and 5B are graphs showing rheological characterization of PNP-1-10 hydrogel formulations with varying concentrations of semaglutide: frequency-dependent oscillatory shear sweep (FIG.5A) and stress-dependent oscillatory shear sweep (FIG.5B). FIGS.6A and 6B are graphs showing rheological characterization of PNP-2-10 hydrogel formulations with varying concentrations of semaglutide: frequency-dependent oscillatory shear sweep (FIG.6A) and stress-dependent oscillatory shear sweep (FIG.6B). FIGS. 7A–7C are graphs showing rheological characterization of PNP-1-10 hydrogel formulations with varying concentrations of tirzepatide: frequency-dependent oscillatory shear sweep (FIGS.7A and 7C) and stress-dependent oscillatory shear sweep (FIG. 7B). FIG. 8A is a schematic illustration of an in vitro release assay of semaglutide from PNP hydrogels immersed in saline over two weeks. In vitro release assays were designed to minimize hydrogel erosion by minimizing the surface area-to-volume of the hydrogel. FIG.8B is a graph of in vitro release profiles showing the % cumulative release of semaglutide from PNP-2-10 formulations at low, medium, and high semaglutide loadings, over the course of two weeks. FIG.8C is a graph of in vitro release profiles showing the % cumulative release of semaglutide from PNP-1-10 formulations at low, medium, and high semaglutide loadings, over the course of two weeks. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO FIG.8D is a graph of in vitro release profiles showing the % cumulative release of semaglutide from various PNP-1-10 hydrogel formulations over the course of two weeks, showing the effect of Tween-20 addition on semaglutide release in the presence of propylene glycol and saline. FIG.8E is a graph of in vitro release profiles showing the % cumulative release of semaglutide from various PNP-1-10 hydrogel formulations over the course of two weeks, showing that there is negligible effect of alpha-cyclodextrin addition on semaglutide release in the presence of propylene glycol and saline. FIG.8F is a graph of in vitro release profiles showing the % cumulative release of semaglutide from various PNP-1-10 hydrogel formulations over the course of two weeks, showing the effect of Tween-20 addition on semaglutide release in the presence of propylene glycol and absence of saline. FIG.8G is a graph of in vitro release profiles showing the % cumulative release of semaglutide from various PNP-1-10 hydrogel formulations, showing the effect of bovine serum albumin (BSA) in the release buffer and in the hydrogel. FIG. 9 is a graph of in vitro release profiles showing the % cumulative release of liraglutide from 1.8 mg / mL PNP-1-10 and PNP-2-10 hydrogel formulations, over the course of two weeks. FIG.10 is a graph illustrating in vitro release profiles showing the % cumulative release of liraglutide and insulin glargine (Lantus) from PNP-1-10 hydrogel formulations, over the course of two weeks. FIG.11 is a schematic illustration of a treatment schedule and timing of blood glucose measurements and serum collection for analysis. Diabetic rats received either a single subcutaneous injection of a semaglutide-loaded PNP hydrogel (PNP-1-10 with 1.8 mg / mL semaglutide and 0.05 wt% Tween-20) or a tirzepatide-loaded PNP hydrogel (PNP-1-10 with 4.5 mg / mL tirzepatide and 0.05 wt% Tween-20), or daily subcutaneous bolus injections of PBS, 20 μg semaglutide, or 50 μg tirzepatide. FIGS. 12A and 12B are graphs illustrating the results of oral glucose tolerance testing before treatment (FIG.12A) and after 6 weeks of treatment (FIG.12B). An oral glucose tolerance test (OGTT) was conducted to group diabetic rats into treatment groups. Rats were Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO fasted before administration of a glucose load by oral gavage. Baseline (fasting) blood glucose measurements were taken before glucose administration and measurements were made at regular intervals thereafter. Blood glucose was measured at –5, 0, 5, 15, 30, 45, 60, and 120 min. Using the area under the curve (AUC), rats with similar glucose tolerance were paired and then randomized into treatment groups. FIG.13 is a graph illustrating the percent change in blood glucose (BG) levels for rats treated with PNP hydrogels versus bolus injections. A single administration of semaglutide PNP or tirzepatide PNP hydrogel reduced the BG of type 2-like diabetic male rats over the course of 6 weeks, compared to daily PBS bolus injections. The plot shows change in BG over 6 weeks following each treatment group regimen (n = 6). FIG.14 is a graph illustrating the percent change in weight for rats treated with PNP hydrogels versus bolus injections. A single administration of semaglutide PNP or tirzepatide PNP hydrogel reduced the overall weight gain in type 2-like diabetic male rats over the course of 6 weeks post treatment, compared to daily PBS bolus injections. The plot shows change in weight over 6 weeks of each treatment group (n = 6). FIG.15 is a graph illustrating pharmacokinetics of a 20 μg daily bolus injection of semaglutide versus a PNP hydrogel (PNP-1-10 with a 1.8 mg / mL semaglutide loading and 0.05 wt% Tween-20) in male diabetic rats (n = 6) over the course of 6 weeks post treatment. FIG.16 is a graph illustrating pharmacokinetics of a 20 μg daily bolus injection of semaglutide versus a PNP hydrogel (PNP-1-10 with a 1.8 mg / mL semaglutide loading and 0.05 wt% Tween-20) over the first 48 hours, overlaid with the 24 hour pharmacokinetics of a 20 μg intravenous (I.V.) and subcutaneous (S.C.) bolus injection in male diabetic rats (n = 6). FIG. 17 shows graphs illustrating an assessment of treatment biocompatibility using blood chemistry to look for negative effects on the liver or kidney and evaluating the effect of treatment on HbA1c. Blood was collected pre- and post-treatment (after 6 weeks). Liver toxicity was assessed through measurement of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin. Kidney toxicity was evaluated by examining creatinine and blood urea nitrogen (BUN) levels. Values for ALT, AST, creatine, and BUN were within the range of healthy rats (defined as the mean ± 2 standard deviations) for both the treatment and control groups. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO DETAILED DESCRIPTION Therapeutic peptides that mimic the activity of naturally occurring peptides may be used for treating a wide variety of diseases and conditions. For example, glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L-cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose- dependent manner. GLP-1 in itself is rapidly degraded, but long-acting GLP-1 receptor agonists (GLP-1 RAs) have been developed for the treatment of type 2 diabetes because of the beneficial effects extending also beyond glucose control. However, patient adherence to antihyperglycemic treatment medications is surprisingly low, described for GLP-1 RA to fall between 29% and 54%, resulting in suboptimal type 2 diabetes management which carries an increased risk of stroke, heart and kidney disease, amputations, and blindness. For drugs with short half-lives, poor compliance with prescribed treatment regimens reduces plasma concentrations to unsuitable levels, and multiple doses are often required to return to therapeutic plasma concentrations. Complex and / or frequent administration of treatment is one hurdle to adherence. Conventionally, GLP-1 RA therapeutics are injected either daily or weekly or taken daily orally, leaving room for technological innovations that enable less frequent administrations, which can reduce patient burden and increase patient compliance. To address these and other challenges, the present technology provides composition and methods for delivery of therapeutic peptides, such as incretin mimetics (e.g., GLP-1 RAs) and / or acylated peptides. In some embodiments, for example, the disclosure provides a composition for treating a disease or condition (e.g., diabetes and / or obesity), where the composition includes a dynamic hydrogel composed of a polymer (e.g., a hydrophobically modified cellulose derivative) and a plurality of nanoparticles (e.g., amphiphilic polymeric nanoparticles). The polymer can be non-covalently crosslinked with the plurality of nanoparticles, thus conferring shear-thinning, self-healing, and / or viscoelastic properties to the dynamic hydrogel. The composition can further include an acylated peptide encapsulated by the dynamic hydrogel, such as an incretin mimetic. In some embodiments, the acylated peptide is encapsulated via hydrophobic interactions between a fatty acid side chain of the acylated peptide and hydrophobic surfaces of the nanoparticles. The acylated peptide can be gradually released from the dynamic hydrogel via erosion of the dynamic hydrogel in vivo. Accordingly, upon administration of the composition to the subject, the composition can provide sustained, Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO controlled release of the acylated peptide over a desired treatment period at a rate that is effective for treating the disease or condition. For example, the compositions herein can be designed to provide continuous delivery of an incretin mimetic for upwards of four months from a single administration to match the cadence with which type 2 diabetes patients typically visit their physician. The embodiments of the present technology can provide numerous advantages compared to conventional therapeutic products and treatment approaches. For instance, conventional hydrogel-based depot technologies typically exhibit several critical shortcomings, including complicated manufacturing, poor formulation stability, challenging administration, burst release that can contribute to poor tolerability of the therapy, and insufficiently slow release to enable appropriately long-acting therapies. In contrast to conventional covalently crosslinked hydrogels, the dynamic hydrogels of the present technology are formed through strong yet dynamic physical interactions. As a result, these materials can address the shortcomings of other hydrogel-based depot technologies by exhibiting: (i) mild formulation requirements favorable for facile formulation with therapeutic peptides such as incretin mimetics, and maintaining drug stability during manufacturing and storage; (ii) shear-thinning properties allowing for straightforward injectability through standard syringes and needles, thus improving patient convenience; (iii) rapid self-healing of hydrogel structure and depot formation to avoid burst release of the drug cargo, thus providing excellent tolerability by maintaining consistent slow release to circumvent undesirable side effects (e.g., gastrointestinal discomfort); (iv) sufficiently high yield stress to form a robust depot that persists under the normal stresses of the subcutaneous space following administration; (v) prolonged delivery of therapeutic cargo allowing for continuous delivery over clinically desirable timeframes; (vi) biodegradability; and / or (vii) non-immunogenicity, as well as not promoting immune responses to the encapsulated cargo. Embodiments of the present disclosure will be described more fully hereinafter with reference to the accompanying drawings in which example embodiments are shown. Embodiments of the claims may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. The examples set forth herein are non-limiting examples and are merely examples among other possible examples. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO The headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed present technology. Embodiments under any one heading may be used in conjunction with embodiments under any other heading. I. Dynamic Hydrogels The present technology utilizes dynamic hydrogels that can serve as a versatile platform for controlled release of therapeutic cargo, such as the therapeutic peptides described in Section II below. In some embodiments, the dynamic hydrogels exhibit dynamic behavior, such as shear-thinning behavior, self-healing behavior, and / or highly tunable viscoelastic mechanical properties. The shear-thinning, self-healing, and / or viscoelastic properties of the dynamic hydrogels can result from non-covalent, supramolecular interactions between the components of the hydrogel (e.g., polymers and nanoparticles, as described further below). The non-covalent interactions can include physical crosslinking, which may encompass various types of crosslinking arising from weak physical interactions such as hydrogen bonding, hydrophobic interactions, ionic interactions, van der Waals interactions, host-guest interactions, crystal formation, physical entanglement, or combinations thereof. The non- covalent interactions can allow for the formation of dynamic, reversible crosslinks between components of the hydrogel that are capable of dissociating and reforming, e.g., spontaneously and / or in response to applied stress. The dynamic hydrogels described herein can provide many advantages for therapeutic applications. For instance, the dynamic hydrogels described herein can exhibit high drug loading capacity, gentle conditions for encapsulation of biologic cargo, sustained delivery of cargo, and / or mechanical tunability. However, unlike traditional covalently crosslinked hydrogels, the dynamic hydrogels herein can be easily administered via techniques such as direct injection, catheter delivery, spreading, or spraying, due to their shear-thinning and / or self-healing properties. Additionally, the dynamic hydrogels herein can exhibit unique dynamic network rearrangements that provide highly tunable release characteristics for the therapeutic cargo. The dynamic hydrogels provided herein can also be synthesized in a straight-forward, cost-effective manner that is easily scalable. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO A. Polymer Nanoparticle Hydrogels In some embodiments, the dynamic hydrogels described herein are polymer nanoparticle (PNP) hydrogels. PNP hydrogels are a type of supramolecular hydrogel formed from non-covalent interactions between polymers and nanoparticles. A PNP hydrogel can self- assemble rapidly upon mixing of a polymer solution with a nanoparticle solution. Self- assembly of the PNP hydrogel network can occur when polymers are linked together by adsorption of segments of the polymer chains onto the surfaces of the nanoparticles through multivalent, transient interactions. PNP hydrogel formation can be an entropy-driven process in which solvent molecules (e.g., water) solvating the polymer chains and nanoparticle surfaces are released into the bulk solution upon binding of the polymer chains to the nanoparticle surfaces, thus producing large gains in translational entropy. The interactions between the polymers and nanoparticle surfaces can be transient and reversible, thus allowing the PNP hydrogel to flow under applied shear stress, followed by rapid self-healing when the stress is relaxed. The PNP hydrogels described herein can be composed of any suitable combination of polymers and nanoparticles that are capable of interacting non-covalently with each other to form crosslinks with the desired dynamic behavior. In some embodiments, the nanoparticle and polymer are selected to have a sufficiently strong affinity to produce efficient crosslinking. That is, the free energy gain (c) resulting from the adsorption of a polymer chain to the surface of a nanoparticle can be greater than or comparable to the thermal energy (kBT). In addition, the average number of interactions per polymer chain and particle can be greater than 2 to achieve percolation of the hydrogel network. Moreover, to favor polymer bridging of multiple nanoparticles (as opposed to polymer wrapping around individual particles), the nanoparticle diameter can be comparable to or less than the persistence length of the polymer chains. When some or all of these criteria are met, the nanoparticles can serve as crosslinkers between the polymer chains, while the polymer chains can bridge many different particles, thus enabling hydrogel formation. In some embodiments, the modulus (G) of the PNP hydrogel is related to the number of dynamic hydrogel interactions per unit volume (n) and the energy associated with each interaction (ĮkBT) according to the following relation: G § nĮkBT. In some embodiments, the nanoparticle surfaces are hydrophobic, such that the adsorption of the polymer chains to the nanoparticle surfaces are at least partially influenced Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO by the general level of hydrophobicity along the polymer chain (e.g., the size and / or number of hydrophobic groups attached to the polymer chain). For example, the PNP hydrogels described herein can utilize polymer-nanoparticle interactions between hydrophobically-modified cellulose derivatives and nanoparticles, such as dodecyl-modified hydroxypropylmethylcellulose (HPMC-C12) and biodegradable polymeric nanoparticles composed of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA). Additional examples of nanoparticles and polymers suitable for use in the PNP hydrogels herein are provided in Sections I.A.1 and I.A.2 below, respectively. The PNP hydrogels described herein can be differentiated from conventional drug delivery systems that include nanoparticles embedded in a covalently crosslinked hydrogel. Such conventional systems typically include gel-forming polymers that are covalently crosslinked with each other to form the gel network, while the nanoparticles serve as an optional additive that plays no role in gel formation, and thus can be freely substituted with other additives or omitted altogether. In contrast, the PNP hydrogels herein may be specifically formed through the interactions between the nanoparticles and polymers. In some embodiments, the polymers and nanoparticles used in the PNP hydrogels herein each independently do not form a gel alone, or are not used at concentrations where the polymer alone or the nanoparticle alone form a gel, such that gel formation occurs only when the polymer and nanoparticle are combined. In some embodiments, the PNP hydrogels herein include one or more polymers combined with one or more nanoparticles, such that the loss modulus of a solution of the one or more polymers and the loss modulus of a solution of the one or more particles are each greater than their respective storage moduli at an angular frequency within a range from 0.1 rad / s to 100 rad / s (e.g., 10 rad / s) as measured by oscillatory shear rheometry in the linear viscoelastic region. The storage modulus of the PNP hydrogel produced by combining the one or more polymers with the one or more particles may be greater than the loss modulus of the PNP hydrogel at an angular frequency within a range from 0.1 rad / s to 100 rad / s (e.g., 10 rad / s) as measured by oscillatory shear rheometry in the linear viscoelastic region. In some embodiments, the dynamic shear viscosity of the PNP hydrogel at a shear rate within a range from 0.1 sí1to 100 sí1(e.g., 10 s-1) is greater than the sum of the dynamic shear viscosity of the solution of the one or more polymers and dynamic shear viscosity of the solution of the one Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO or more nanoparticles at the shear rate within the range from 0.1 sí1to 100 sí1. For example, the dynamic shear viscosity of the PNP hydrogel can be greater than the sum of the dynamic shear viscosities of the polymer solution and the nanoparticle solution by a multiplicative factor within a range from 2 to 100,000, 2 to 1000, 2 to 100, or 2 to 10. The PNP hydrogels described herein can include any concentration of polymers and nanoparticles suitable for providing desired hydrogel properties. For instance, higher polymer concentrations can produce PNP hydrogels with a higher stiffness and / or slower degradation rate. Higher nanoparticle concentrations can produce PNP hydrogels with a higher viscosity, stiffness, and yield stress, and / or slower degradation rate. The hydrogel properties may depend not only on the overall amount of solid content in the hydrogel, but also on the stoichiometry of polymer content to nanoparticle content. For example, increasing the nanoparticle concentration at a constant polymer concentration can produce a hydrogel having a more solid-like rheological response (e.g., lower tan delta), increased strain-to-yield, and increased yield stress. Increasing the polymer concentration at a constant nanoparticle concentration can produce a hydrogel having a more liquid-like rheological response (e.g., higher tan delta and greater frequency dependency of the storage modulus) and reduced strain- to-yield. In some embodiments, the PNP hydrogels described herein include at least 0.25 wt%, 0.5 wt%, 0.75 wt%, 1 wt%, 1.5 wt%, 2 wt%, 2.5 wt%, 3 wt%, 3.5 wt%, 4 wt%, 4.5 wt%, or 5 wt % polymer; and / or at least 0.5 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 12 wt%, or 15 wt% nanoparticles. Alternatively or in combination, the concentration of polymer within the PNP hydrogel can be within a range from 0.5 wt% to 5 wt%, 0.5 wt% to 4 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1 wt%, 1 wt% to 5 wt%, 1 wt% to 4 wt%, 1 wt% to 3 wt%, 1 wt% to 2 wt%, 2 wt% to 5 wt%, 2 wt% to 4 wt%, 2 wt% to 3 wt%, 3 wt% to 5 wt%, 3 wt% to 4 wt%, or 4 wt% to 5 wt%; and / or the concentration of nanoparticles within the PNP hydrogel can be within a range from 1 wt% to 12 wt%, 1 wt% to 10 wt%, 1 wt% to 8 wt%, 1 wt% to 5 wt%, 1 wt% to 3 wt%, 3 wt% to 12 wt%, 3 wt% to 10 wt%, 3 wt% to 8 wt%, 3 wt% to 5 wt%, 5 wt % to 12 wt%, 5 wt% to 10 wt%, 5 wt% to 8 wt%, 8 wt% to 12 wt%, 8 wt% to 10 wt%, or 10 wt% to 12 wt%. The nomenclature “X-Y hydrogel” or “X:Y hydrogel” is used herein to refer to a hydrogel having X wt% polymer and Y wt% nanoparticles. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO In some embodiments, the PNP hydrogels herein are prepared by simple mixing of the polymers, nanoparticles, therapeutic cargo, and any optional additives. For example, the PNP hydrogel can be prepared by forming a polymer solution (e.g., by dissolving the polymer in an aqueous solvent such as water or a buffered solution such as phosphate-buffered saline (PBS)), forming a nanoparticle solution (e.g., by suspending the nanoparticles in an aqueous solvent), and forming a solution containing the therapeutic cargo (e.g., by dissolving or suspending the therapeutic cargo in an aqueous solvent). The solutions can then be combined, optionally with external agitation, to form the PNP hydrogel including the therapeutic cargo. 1. Nanoparticles The PNP hydrogels described herein can include a plurality of nanoparticles. The nanoparticles can be any suitable shape, such as spheres, cubes, rods, tubes, plates, fibers, etc. The nanoparticles can have a mean particle size (e.g., diameter) within a range from 1 nm to 1000 nm, 1 nm to 500 nm, 1 nm to 250 nm, 1 nm to 150 nm, 1 nm to 100 nm, 1 nm to 50 nm, 1 nm to 25 nm, 1 nm to 10 nm, 10 nm to 1000 nm, 10 nm to 500 nm, 10 nm to 250 nm, 10 nm to 150 nm, 10 nm to 100 nm, 10 nm to 50 nm, 10 nm to 25 nm, 25 nm to 1000 nm, 25 nm to 500 nm, 25 nm to 250 nm, 25 nm to 150 nm, 25 nm to 100 nm, 25 nm to 50 nm, 50 nm to 1000 nm, 50 nm to 500 nm, 50 nm to 250 nm, 50 nm to 150 nm, 50 nm to 100 nm, 100 nm to 1000 nm, 100 nm to 500 nm, 100 nm to 250 nm, 100 nm to 150 nm, 150 nm to 1000 nm, 150 nm to 500 nm, 150 nm to 250 nm, 250 nm to 1000 nm, 250 m to 500 nm, or 500 nm to 1000 nm. In some embodiments, the nanoparticles have a mean particle size less than or equal to 500 nm, 250 nm, 150 nm, 140 nm, 130 nm, 120 nm, 110 nm, 100 nm, 90 nm, 80 nm, 70 nm, 60 nm, 50 nm, 40 nm, 30 nm, 20 nm, or 10 nm. As described herein, to facilitate hydrogel formation, the mean particle size of the nanoparticles can be similar to or less than the persistence length of the polymer in the PNP hydrogel, such as less than or equal to 125%, 110%, 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% of the persistence length of the polymer. As used herein, “mean particle size” may refer to the statistical mean particle size (e.g., diameter) of the particles in the PNP hydrogel composition. The diameter of an essentially spherical particle may refer to the physical or hydrodynamic diameter. The diameter of a non-spherical particle may refer to the hydrodynamic diameter or to the largest linear distance between two points on the surface of the particle. Mean particle size can be measured using methods known in the art, such as dynamic light scattering. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO The nanoparticles can be made out of a single material or can be made out of a combination of multiple different materials (e.g., two, three, four, five, or more different materials). The material(s) can be biodegradable and / or biocompatible. For example, in some embodiments, the nanoparticles are made partially or entirely out of one or more biodegradable and / or biocompatible polymers. Generally, biodegradable polymers can degrade by enzymatic hydrolysis, exposure to water in vivo, surface erosion, and / or bulk erosion. Biodegradable polymers can include synthetic polymers, naturally occurring polymers, or combinations thereof. Examples of synthetic biodegradable polymers include polyhydroxy acids (e.g., poly(lactic acid), poly(glycolic acid)), polyanhydrides, poly(ortho)esters, polyesters, polyurethanes, poly(butyric acid), poly(valeric acid), poly(caprolactone), poly(hydroxybutyrate), poly(lactide-co-glycolide), poly(lactide-co-caprolactone), poly(ethylene-co-maleic anhydride), poly(ethylene maleic anhydride-co-L-dopamine), poly(ethylene maleic anhydride-co-phenylalanine), poly(ethylene maleic anhydride-co- tyrosine), poly(butadiene-co-maleic anhydride), poly(butadiene maleic anhydride-co-L- dopamine) (pBMAD), poly(butadiene maleic anhydride-co-phenylalanine), poly(butadiene maleic anhydride-co-tyrosine), and combinations (e.g., mixtures, copolymers) thereof. Examples of naturally occurring biodegradable polymers include polysaccharides (e.g., cellulose, alginate, collagen, chitosan, hyaluronic acid, starch, agarose, agar, xanthan gum), proteins (e.g., collagen, fibrin, albumin, zein, gelatin), and derivatives thereof (e.g., derivatives of cellulose such as cellulose nanocrystals, cellulose nanofibers), and combinations thereof. Alternatively or in combination, the nanoparticles can be made partially or entirely out of one or more non-biodegradable polymers. Examples of non-biodegradable polymers include polystyrenes, polyalkylene glycols, poly(meth)acrylates, poly (meth)acrylamides, polyalkylenes (e.g., polyethylene, polyvinyls, poly(vinyl acetate), poly(ethylene terephthalate)), and combinations thereof. The polymer(s) used to form the nanoparticles herein can have any suitable molecular weight, such as a molecular weight (e.g., number-average molecular weight (Mn)) within a range from 500 Da to 10,000 kDa, 1 kDa to 1000 kDa, or 10 kDa to 100 kDa. As used herein, “molecular weight” may refer to the relative average chain length of the bulk polymer, and can be estimated or characterized in various ways including gel permeation chromatography (GPC) and capillary viscometry. GPC molecular weights are reported as the Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO number-average molecular weight (Mn) as opposed to the weight-average molecular weight (Mw). Capillary viscometry provides estimates of molecular weight (Mv) as the inherent viscosity determined from a dilute polymer solution using a particular set of concentration, temperature, and solvent conditions. In some embodiments, the nanoparticles are made partially or entirely out of one or more inorganic materials, such as clays (e.g., silicates) or other types of minerals (e.g., sulfides, oxides, halides, carbonates, sulfates, phosphates, apatites), or combinations thereof. Alternatively or in combination, the nanoparticles can be made partially or entirely out of made of one or more metals, such as gold, silver, copper, platinum, palladium, ruthenium, or combinations thereof. Optionally, the nanoparticles can be made partially or entirely out of carbon nanotubes (e.g., single-walled or multi-walled nanotubes), graphene, graphene oxide, or other ultrathin single crystals, including black phosphorous and boron based nanosheets. In some embodiments, the nanoparticles are core-shell particles (also known as “core-corona particles”). A core-shell particle can have a core containing or formed from a first material, and a shell or corona containing or formed from a second, different material. For example, a core-shell particle can include at least two polymers, such that the core is made from a first polymer, and the shell or corona is made from a second, different polymer. As another example, the core-shell particle can include a single block copolymer, such that the core is made from a first block of the block copolymer, and the shell or corona can be made from a second block of the block copolymer. In some embodiments, one or both of the components of the core-shell particle is a non-polymeric material. A core-shell particle can be composed of two compositionally disparate phases, of which one (either the core or shell / corona) is hydrophobic and the other (core or shell / corona) is hydrophilic. Suitable hydrophobic components include polyamides (e.g., poly(amino acids)), polyesters (e.g., poly(lactic acid), poly(caprolactone)), polypropylene oxides, polystyrenes, and combinations thereof. Suitable hydrophilic components include polysaccharides, proteins, polyamides (e.g., poly(amino acids)), naturally occurring polymers, synthetic polymers, and combinations thereof. Suitable block copolymers include combinations of polyethylene glycol and polyesters (e.g., PEG-PLA, poly(ethylene glycol)- block-poly(caprolactone) (PEG-PCL)) and combinations of polyethylene glycol and polypropylene glycol (e.g., poloxamers). In some embodiments, the core-shell particle is Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO composed of an amphiphilic polymer including (1) one or more hydrophobic polymers selected from polyanhydrides, poly(ortho)esters, polyesters, polyurethanes, and / or copolymers thereof, and (2) one or more hydrophilic polymers selected from polysaccharides, proteins, poly(amino acids), and / or polyalkylene oxides. Alternatively, the nanoparticles can be homogenous nanoparticles. A homogenous nanoparticle can be uniformly formed from a single material, or can be formed from multiple materials that are not separated into disparate phases within the particle as in core-shell particles. The nanoparticles can be prepared using techniques known in the art. The technique to be used can depend on a variety of factors, including the materials used to form the nanoparticles, the desired size range of the resulting nanoparticles, and suitability for the material to be encapsulated. Examples of suitable techniques include, but are not limited to, solvent evaporation, solvent removal, hot melt microencapsulation, spray drying, phase inversion, polyelectrolyte condensation, single and double emulsion (e.g., probe sonication), nanoparticle molding, and electrostatic self-assembly. The concentration of the nanoparticles in the PNP hydrogel can be varied to produce the desired hydrogel properties. In some embodiments, for example, the concentration of the nanoparticles in the PNP hydrogel is within a range from 1 wt% to 15 wt%, 2 wt% to 12 wt%, 3 wt% to 10 wt%, 5 wt% to 8 wt%, 5 wt% to 15 wt%, 5 wt% to 10 wt%, 10 wt% to 15wt%, or 10 wt% to 12 wt%. The concentration of the nanoparticles in the PNP hydrogel can be about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, about 10 wt%, about 11 wt%, about 12 wt%, about 13 wt%, about 14 wt%, or about 15 wt%. In some embodiments, the concentration of the nanoparticles in the PNP hydrogel can be greater than or equal to 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, or 14 wt%. Alternatively or in combination, the concentration of the nanoparticles in the PNP hydrogel can be less than or equal to 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, or 15 wt%. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Polymers The PNP hydrogel can be formed when the nanoparticles are mixed with and interact with one or more polymers. The shear-thinning and / or self-healing properties of the PNP hydrogel can be derived from reversible, non-covalent interactions between the nanoparticles and the polymer chains, as described herein. The PNP hydrogel can include a single type of polymer or can include a combination of multiple different polymers (e.g., two, three, four, five, or more different polymers). The polymer(s) can be biodegradable and / or biocompatible. The polymer(s) can include naturally occurring polymers, synthetic polymers, or derivatives or combinations thereof. Examples of naturally occurring polymers include polysaccharides (e.g., cellulose, alginate, collagen, chitosan, hyaluronic acid, starch, agarose, agar, xanthan gum), proteins (e.g., collagen, fibrin, albumin, zein, gelatin), and combinations thereof. Examples of synthetic polymers include polyacrylamide, poly(lactic acid), polyethylene glycol, polyethylene glycol-co-propylene glycol (PEO-PPO), poly(acrylates) (e.g., poly(2-hydroxyethyl methacrylate)), and combinations thereof. In some embodiments, the PNP hydrogel includes a derivative of a naturally occurring polymer, such as a cellulose derivative. Examples of cellulose derivatives include hydroxypropylmethylcellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropylcellulose (HPC), ethylcellulose (EC), methylcellulose (MC), hydroxyethylmethylcellulose (HEMC), carboxymethylcellulose (CMC), carboxymethyl ethyl cellulose (CMEC), and combinations thereof. In some embodiments, the PNP hydrogels herein include at least one polymer that is modified with a hydrophobic moiety. Hydrophobic modification of polymers may increase the energy associated with each polymer nanoparticle interaction (ĮkBT), thereby increasing the modulus of the dynamic hydrogel given the same number of interactions per unit volume. Such modification may facilitate favorable interactions between the hydrophobic moiety on the polymer chain and the hydrophobic core of the nanoparticle, thereby enhancing the adsorption energy of the polymer to the nanoparticles. The hydrophobic moiety can include a plurality of carbon atoms (e.g., from 2 to 50 carbon atoms, from 2 to 30 carbon atoms, or from 2 to 18 carbon atoms), and can be a saturated molecule or an unsaturated molecule. Examples of hydrophobic moieties that may be used include, but are not limited to, alkyl moieties (e.g., C4 to C18 alkyls, such as butyl (–C4), hexyl (–C6), octyl (–C8), decyl (–C10), dodecyl (–C12), tetradecyl (–C14), pentadecyl (–C15), hexadecyl (–C16), heptadecyl (–C17), Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO octadecyl (–C18)), alkenyl moieties (e.g., oleyl, linoleyl), aryl moieties (e.g., phenyl, benzyl, pyryl, naphthyl, anthracene), and cycloalkyl moieties (e.g., adamantyl, cyclohexyl, cholesterol). In some embodiments, the degree of modification of the polymer (e.g., percentage of reactive groups on the polymer have been functionalized with the hydrophobic moiety) is within a range from 1% to 50%, 5% to 30%, 5% to 25%, or 10% to 15%. For example, the degree of modification can be about 5%, 10%, 15%, 20%, or 25%. The concentration of the polymer(s) in the PNP hydrogel can be varied to produce the desired hydrogel properties (e.g., stiffness, storage modulus, degradation rate). In some embodiments, for example, the concentration of the polymer(s) in the PNP hydrogel is within a range from 0.25 wt% to 10 wt%, 0.5 wt% to 5 wt%, 0.5 wt% to 2 wt%, 1 wt% to 5 wt%, or 1 wt% to 2 wt%. The concentration of the polymer(s) in the PNP hydrogel can be about 0.1 wt%, 0.25 wt%, 0.5 wt% 0.75 wt%, 1 wt%, 1.25 wt%, 1.5 wt%, 1.75 wt%, 2 wt%, 2.25 wt%, 2.5 wt%, 2.75 wt%, 3 wt%, 3.5 wt%, 4 wt%, 4.5 wt%, or 5 wt%. In some embodiments, the concentration of the polymer(s) in the PNP hydrogel can be greater than or equal to 0.25 wt%, 0.5 wt% 0.75 wt%, 1 wt%, 1.25 wt%, 1.5 wt%, 1.75 wt%, 2 wt%, 2.25 wt%, 2.5 wt%, 2.75 wt%, 3 wt%, 3.5 wt%, 4 wt%, 4.5 wt%. Alternatively or in combination, the concentration of the polymer(s) in the PNP hydrogel can be less than or equal to 0.5 wt% 0.75 wt%, 1 wt%, 1.25 wt%, 1.5 wt%, 1.75 wt%, 2 wt%, 2.25 wt%, 2.5 wt%, 2.75 wt%, 3 wt%, 3.5 wt%, 4 wt%, 4.5 wt%, or 5 wt%. 3. Additional Components The PNP hydrogels herein can optionally include one or more additional components to facilitate gel formation and / or modify the properties of the hydrogel. For example, the PNP hydrogels herein can include at least one enhancer compound that enhances the interactions between the polymers and nanoparticles, e.g., by providing bridging-type non- covalent interactions between the polymers and nanoparticles. In some embodiments, a portion of an enhancer compound interacts non-covalently with the polymer and a second portion of the enhancer compound interacts non-covalently with the nanoparticle. Non-limiting examples of such interactions include ionic interactions such as cationic / anionic interactions, electrostatic interactions, and hydrogen bonding interactions. For example, in embodiments where the polymer is negatively charged at physiological pH (e.g., hyaluronic acid, carboxymethyl cellulose), a cationic surfactant can be Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO used to enhance adsorption of the anionic polymer to the nanoparticles via electrostatic interactions. Examples of positively charged surfactants include cetyltrimethylammonium bromide (CTAB), cetyltrimethylammonium iodide, cetyltrimethylammonium fluoride, and cetyltrimethylammonium chloride. Conversely, in embodiments where the polymer is positively charged at physiological pH (e.g., chitosan, aminopolysaccharides, poly(lysine), cationic acrylate polymers, cationic vinyl polymers), an anionic surfactant can be used to enhance adsorption of the cationic polymer to the nanoparticles via electrostatic interactions. Examples of negatively charged surfactants include sodium dodecyl sulfate, sodium stearate, and charged fatty acid surfactants. In some embodiments, molecular recognition between at least two compounds can provide the enhancement. For example, the adsorption of polymers, such as polysaccharides, to nanoparticles can be enhanced by an enhancer compound which includes a carbohydrate in one portion of the enhancer and a polymer tail that interacts with the nanoparticle. The concentration of the enhancer compound can be varied to produce the desired effect on hydrogel formation. In some embodiments, for example, the concentration of the enhancer compound in the PNP hydrogel is within a range from 0.25 wt% to 10 wt%, 0.5 wt% to 5 wt%, 0.5 wt% to 2 wt%, 1 wt% to 5 wt%, or 1 wt% to 2 wt%. The concentration of the enhancer compound in the PNP hydrogel can be about 0.1 wt%, 0.25 wt%, 0.5 wt% 0.75 wt%, 1 wt%, 1.25 wt%, 1.5 wt%, 1.75 wt%, 2 wt%, 2.25 wt%, 2.5 wt%, 2.75 wt%, 3 wt%, 3.5 wt%, 4 wt%, 4.5 wt%, or 5 wt%. In some embodiments, the concentration of the enhancer compound in the PNP hydrogel can be greater than or equal to 0.25 wt%, 0.5 wt% 0.75 wt%, 1 wt%, 1.25 wt%, 1.5 wt%, 1.75 wt%, 2 wt%, 2.25 wt%, 2.5 wt%, 2.75 wt%, 3 wt%, 3.5 wt%, 4 wt%, 4.5 wt%. Alternatively or in combination, the concentration of the enhancer compound in the PNP hydrogel can be less than or equal to 0.5 wt% 0.75 wt%, 1 wt%, 1.25 wt%, 1.5 wt%, 1.75 wt%, 2 wt%, 2.25 wt%, 2.5 wt%, 2.75 wt%, 3 wt%, 3.5 wt%, 4 wt%, 4.5 wt%, or 5 wt%. Optionally, the PNP hydrogel may not include any enhancer compounds. B. Hydrogel Properties The dynamic hydrogels described herein (e.g., the PNP hydrogels of Section I.A) can exhibit favorable physical and biological properties that contribute to their efficacy as drug delivery platforms. The properties of the dynamic hydrogels herein can be tuned in various Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO ways, such as by modifying the types of components used to form the hydrogel (e.g., polymers, nanoparticles, and / or additional components as previously described in Section I.A; and / or the therapeutic cargo carried by the hydrogel as described below in Section II), the concentrations of the components, and / or the chemical functionalities of the components. Accordingly, the properties of the dynamic hydrogels herein can be adapted to the particular therapeutic application, such as forming a stable and / or persistent depot when delivered in vivo, providing a desired release profile for the therapeutic cargo (e.g., short-term release versus long-term release), providing a desired release mechanism for the therapeutic cargo (e.g., diffusion-based release versus erosion-based release), compatibility with a desired route of administration (e.g., injecting, infusing, spraying, spreading), biodegradability, biocompatibility, and / or allowing for cellular infiltration. Any reference herein to a property of a dynamic hydrogel may refer to the property of the dynamic hydrogel without any therapeutic cargo (e.g., a PNP hydrogel composed only of polymers and nanoparticles), the property of the dynamic hydrogel including the therapeutic cargo (e.g., a PNP hydrogel including polymers, nanoparticles, and the encapsulated therapeutic cargo), or both, unless otherwise stated or otherwise evident from the context. The storage modulus (G') of the dynamic hydrogel can correlate to the overall stiffness of the hydrogel, which in turn can dictate the time scale of degradation of the hydrogel (e.g., hydrogels having a higher storage modulus may be stiffer and degrade more slowly than gels having a lower storage modulus). Accordingly, in embodiments where the therapeutic cargo of the dynamic hydrogel is released primarily or entirely via an erosion-based mechanism, the release rate of the therapeutic cargo can be tuned by adjusting the storage modulus of the hydrogel (e.g., a higher storage modulus can produce a slower degradation rate and thus a slower release rate of the therapeutic cargo, while a lower storage modulus can produce a higher degradation rate and thus a faster release rate of the therapeutic cargo). For example, in embodiments where the dynamic hydrogel is a PNP hydrogel, the storage modulus of the PNP hydrogel can be increased or decreased by increasing or decreasing the polymer concentration, and / or by increasing or decreasing the nanoparticle concentration. In some embodiments, the dynamic hydrogels herein have a storage modulus within a range from 1 Pa to 10,000 Pa, 1 Pa to 5000 Pa, 1 Pa to 2500 Pa, 1 Pa to 1000 Pa, 1 Pa to 500 Pa, 1 Pa to 200 Pa, 1 Pa to 10 Pa, 10 Pa to 10,000 Pa, 10 Pa to 5000 Pa, 10 Pa to 2500 Pa, 10 Pa to 1000 Pa, 10 Pa to 500 Pa, 10 Pa to 200 Pa, 10 Pa to 100 Pa, 10 Pa to 50 Pa, 50 P to 10,000 Pa, 50 Pa to Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 5000 Pa, 50 Pa to 2500 Pa, 50 Pa to 1000 Pa, 50 Pa to 500 Pa, 50 Pa to 200 Pa, 50 Pa to 100 Pa, 100 Pa to 10,000 Pa, 100 Pa to 5000 Pa, 100 Pa to 2500 Pa, 100 Pa to 1000 Pa, 100 Pa to 500 Pa, 100 Pa to 200 Pa, 200 Pa to 10,000 Pa, 200 Pa to 5000 Pa, 200 Pa to 2500 Pa, 200 Pa to 1000 Pa, 200 Pa to 500 Pa, 500 Pa to 10,000 Pa, 500 Pa to 5000 Pa, 500 Pa to 2500 Pa, 500 Pa to 1000 Pa, 1000 Pa to 10,000 Pa, 1000 Pa to 5000 Pa, 1000 Pa to 2500 Pa, 2500 Pa to 10,000 Pa, 2500 Pa to 5000 Pa, or 5000 Pa to 10,000 Pa. The storage modulus can be measured, for example, using an oscillatory shear test in a parallel plate rheometer at an angular frequency of 10 rad / s, a strain within the linear viscoelastic region of the hydrogel (e.g., 1% strain), and a temperature of 25 °C. The yield stress (IJy) of the dynamic hydrogel can correlate to the ability of the hydrogel to form and maintain a cohesive depot in vivo (e.g., materials lacking a yield stress may flow rather than forming a cohesive depot). The dynamic hydrogels herein can exhibit little or no flow when subjected to stresses below the yield stress. When subjected to stresses above the yield stress, the dynamic hydrogels can flow, corresponding to a significant drop in observed viscosity (e.g., a decrease of at least one or two orders of magnitude). In embodiments where the dynamic hydrogel is a PNP hydrogel, the yield stress can be increased or decreased by increasing or decreasing the nanoparticle concentration, respectively. In some embodiments, the dynamic hydrogels herein have a yield stress within a range from 0.1 Pa to 1000 Pa, 0.1 Pa to 500 Pa, 0.1 Pa to 200 Pa, 0.1 Pa to 100 Pa, 0.1 Pa to 50 Pa, 0.1 Pa to 20 Pa, 0.1 Pa to 10 Pa, 0.1 Pa to 1 Pa, 1 Pa to 1000 Pa, 1 Pa to 500 Pa, 1 Pa to 200 Pa, 1 Pa to 100 Pa, 1 Pa to 50 Pa, 1 Pa to 10 Pa, 10 Pa to 1000 Pa, 10 Pa to 500 Pa, 10 Pa to 200 Pa, 10 Pa to 100 Pa, 10 Pa to 50 Pa, 10 Pa to 20 Pa, 20 Pa to 1000 Pa, 20 Pa to 500 Pa, 20 Pa to 200 Pa, 20 Pa to 100 Pa, 20 Pa to 50 Pa, 50 Pa to 1000 Pa, 50 Pa to 500 Pa, 50 Pa to 200 Pa, 50 Pa to 100 Pa, 100 Pa to 500 Pa, 100 Pa to 200 Pa, 200 Pa to 1000 Pa, 200 Pa to 500 Pa, or 500 Pa to 1000 Pa. The yield stress can be measured, for example, using a stress ramp or stress sweep (e.g., from 1 Pa to 100 Pa, or from 1 Pa to 1000 Pa) in a parallel plate rheometer at a temperature of 25 °C to identify the stress at which the hydrogel exhibits a drop in viscosity. The tan delta of the dynamic hydrogel (the ratio of the loss modulus (G'') over the storage modulus (G') (tan(į) = G'' / G')) can describe the overall viscoelasticity of the hydrogel (e.g., lower tan delta values correspond to more solid-like behavior, higher tan delta values correspond to more liquid-like behavior), and can correlate to the degradation rate of Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO the hydrogel. In some embodiments, the dynamic hydrogels herein have a tan delta less than or equal to 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, or 0.1. The tan delta can be within a range from 0.1 to 1, 0.1 to 0.5, 0.1 to 0.3, 0.2 to 1, 0.2 to 0.5, or 0.5 to 1. The tan delta can be measured, for example, using an oscillatory shear test in a parallel plate rheometer at an angular frequency of 10 rad / s, a strain within the linear viscoelastic region of the hydrogel (e.g., 1% strain), and a temperature of 25 °C. In some embodiments, the dynamic hydrogels herein exhibit shear-thinning behavior, in that the viscosity of the dynamic hydrogel decreases with increasing shear rate and / or shear stress. Shear-thinning behavior can be advantageous, for example, to allow the dynamic hydrogel to be administered via injection. In some embodiments, the viscosity of the gel decreases with increasing shear rate at a shear rate within a range from 0.1 s-1to 1000 s-1, for example, as observed on an oscillatory rheometer (e.g., a parallel plate rheometer) at 25 ºC. In some embodiments, the dynamic hydrogels herein have a viscosity within a range from 10 mPa-s to 2000 mPa-s, 10 mPa-s to 1000 mPa-s, 10 mPa-s to 500 mPa-s, 10 mPa-s to 200 mPa- s, 10 mPa-s to 100 mPa-s, 10 mPa-s to 50 mPa-s, 50 mPa-s to 2000 mPa-s, 50 mPa-s to 1000 mPa-s, 50 mPa-s to 500 mPa-s, 50 mPa-s to 200 mPa-s, 50 mPa-s to 100 mPa-s, 100 mPa-s to 2000 mPa-s, 100 mPa-s to 1000 mPa-s, 100 mPa-s to 500 mPa-s, 100 mPa-s to 200 mPa-s, 200 mPa-s to 2000 mPa-s, 200 mPa-s to 1000 mPa-s, 200 mPa-s to 500 mPa-s, 500 mPa-s to 2000 mPa-s, 500 mPa-s to 1000 mPa-s, or 1000 mPa-s to 2000 mPa-s at a shear rate of 1000 s-1. The viscosity can be measured, for example, using steady shear measurements in a parallel plate rheometer at a temperature of 25 ºC. In some embodiments, the dynamic hydrogels herein exhibit self-healing behavior. Self-healing may refer to a process in which a gel that exhibits reduced resistance to flow when subjected to an external stress regains some or all of its rigidity and / or strength after the external stress is removed. Self-healing behavior can be advantageous, for example, to allow the dynamic hydrogel to form a cohesive depot after administration via injection and / or to limit burst release. In some embodiments, the dynamic hydrogels herein stop flowing and recover their mechanical properties in no more than 5 seconds, 10 seconds, 30 seconds, 1 minute, 2 minutes, 3 minutes, 5 minutes, or 10 minutes after the external stress is removed. Optionally, the modulus and / or viscosity of the dynamic hydrogel can recover to at least 90% of the initial value before application of the external stress within 5 minutes in a step-strain Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO measurement (conducted with strains of 0.5% and 500%) or step-shear measurement (conducted with shear rates of 0.1 s-1and 100-1), respectively, on an oscillatory rheometer. In some embodiments, the dynamic hydrogels herein exhibit viscoelastic behavior, in that the storage modulus (G’) of the hydrogel is dominant over the loss modulus (G”) at some point, for example, as observed in an oscillatory frequency sweep measurement in a range from 0.1 rad / s to 100 rad / s on an oscillatory rheometer performed in the linear viscoelastic region, yet the hydrogel exhibits complete stress relaxation following application of a constant strain of 500% within 15 minutes. In some embodiments, the dynamic hydrogels described herein are biocompatible. A biocompatible material can be a material that is, along with any metabolites or degradation products thereof, generally non-toxic to the subject, and do not cause any significant adverse effects to the subject, at concentrations resulting from the degradation of the administered materials. A biocompatible material can be a material that does not elicit a significant inflammatory or immune response when administered to a subject. In some embodiments, the dynamic hydrogels described herein are biodegradable. A biodegradable material can be a material that will degrade or erode under physiological conditions to smaller units or chemical species that are capable of being metabolized, eliminated, or excreted by the subject. For example, upon in vivo administration to a subject, the dynamic hydrogel can dissolve as the non-covalent bonds dissociate. The degradation rate of the dynamic hydrogel can be varied as desired, e.g., depending on the desired release profile for the therapeutic cargo. In some embodiments, following in vivo administration, the dynamic hydrogels are designed to persist at the administration site (e.g., remain as a cohesive depot) for at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 21 days, 28 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 9 months, or 12 months. Alternatively or in combination, the dynamic hydrogels herein can persist at the administration site for no more than 12 months, 9 months, 6 months, 5 months, 4 months, 3 months, 2 months, 1 month, 28 days, 21 days, 14 days, 13 days, 12 days, 11 days, 10 days, 9 days, 8 days, 7 days, 6 days, 5 days, 4 days, 3 days, 2 days, or 1 day. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO II. Compositions for Delivery of Therapeutic Peptides and Associated Methods In some embodiments, the present technology provides compositions for delivery of therapeutic peptides for treating a disease or condition in a subject. The composition can include a dynamic hydrogel and at least one therapeutic peptide carried by the dynamic hydrogel. The dynamic hydrogel can encapsulate the therapeutic peptide and provide sustained, controlled release of the therapeutic peptide when the composition is administered to a subject. In some embodiments, the dynamic hydrogel exhibits shear-thinning behavior that allows for facile administration via injection, as well as self-healing behavior that allows for formation of a cohesive depot that delivers the therapeutic peptide over a prolonged treatment period. For example, FIG. 1A is a schematic illustration of a PNP hydrogel prepared by mixing of hydrophobically-modified HPMC with PEG-PLA nanoparticles that allows for facile encapsulation of a therapeutic peptide, and FIG.1B is a schematic illustration of formation of a localized depot in the subcutaneous space following subcutaneous injection of the PNP hydrogel, thus providing a tunable platform for sustained release of the therapeutic peptide. A. Therapeutic Peptides 1. Incretin Mimetics In some embodiments, the therapeutic peptide is an incretin mimetic. Incretin mimetics are compounds that mimic the activity of incretin hormones. Incretin hormones are peptides that are secreted by the gut in response to nutrient ingestion. The primary incretin hormones are GLP-1 and gastric inhibitory peptide (GIP). GLP-1 contributes to the regulation of glucose homeostasis within the body through its interaction with the GLP-1 receptor. GLP- 1 is secreted from intestinal L-cells in response to nutrients and lowers blood glucose by stimulating insulin and suppressing glucagon secretion in a glucose-dependent manner, reducing the risk of hypoglycemia. In addition, GLP-1 is also a neurotransmitter synthesized by preproglucagon neurons in the brain and acts via central pathways to lower energy intake through an effect on satiety, hunger, and reward-related measures, leading to a lowering of body weight. Metabolic effects of GLP-1 include glucose-dependent stimulation of insulin secretion, inhibition of glucagon secretion, inhibition of food intake, decrease of gastric emptying, and increase of natriuresis and diuresis. GLP-1 has also been shown to influence learning, memory, reward behavior, and palatability, as well as to exhibit neuroprotective, Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO cardioprotective, and anti-inflammatory effects. However, the therapeutic applicability of native GLP-1 is limited by its short half-life in vivo (approximately 2 to 3 minutes) and inactivation by the enzyme dipeptidyl peptidase 4 (DPP4). GIP is secreted by enteroendocrine K-cells in response to nutrients and also exhibits an insulinotropic effect via binding to the GIP receptor. However, unlike GLP-1, GIP stimulates glucagon secretion. GIP also influences appetite, fat accumulation, memory, and bone formation. Native GIP also exhibits a short half- life (approximately 4 to 5 minutes) and is inactivated by DPP4. In some embodiments, the incretin mimetic is a GLP-1 RA. GLP-1 RAs (also known as “GLP-1 analogues”) are a class of drugs that interact with the GLP-1 receptor and display structural similarities to native GLP-1, but with modifications to extend the in vivo half-life and thus provide improved bioavailability. GLP-1 RAs can be categorized as either short-acting or long-acting compounds. Short-acting GLP-1 RAs have been rendered resistant to cleavage by DPP4 by altering the amino acids at the second and third N-terminal positions, but are still subject to renal elimination and thus generally have a half-life from approximately 2 to 5 hours. Examples of short-acting GLP-1 RAs include exenatide and lixisenatide. Long- acting GLP-1 RAs implement mechanisms to reduce renal elimination, such as acylation with fatty acids to facilitate binding to serum albumin or conjugation to a larger molecule / component, and thus can have a half-life from 12 hours to several days. Examples of long-acting GLP-1 RAs include liraglutide (acylation with C16 fatty monoacid), semaglutide (acylation with C18 fatty diacid), tirzepatide (acylation with C20 fatty diacid), retatrutide (acylation with C20 fatty diacid), albiglutide (conjugation to albumin), dulaglutide (conjugation to Fc fragment of IgG), and exenatide-LAR (long-acting release) (coupled to biodegradable polymer microspheres). The GLP-1 RA can include a peptide that binds to the GLP-1 receptor. The peptide can be an analogue of a native GLP-1 peptide, such as the endogenous human GLP-1 peptide (e.g., GLP-1 (7-36) or GLP-1 (7-37)). For example, the peptide of the GLP-1 RA can include a sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99%, or 100% sequence identity to any one of SEQ ID NO: 1 or SEQ ID NO: 2. The peptide can be produced in suitable host cells via recombinant DNA technology, can be produced in a cell- free system, or can be produced synthetically via solid phase synthesis. Table 1: GLP-1 Peptides Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO In some embodiments, the GLP-1 RA is a mono-receptor agonist that binds exclusively to the GLP-1 receptor. Examples of GLP-1 mono-receptor agonists include exenatide, exenatide-LAR, lixisenatide, liraglutide, semaglutide, albiglutide, dulaglutide, efpeglenatide, and ecnoglutide. The peptide of the GLP-1 mono-receptor agonist can be an analogue of a native GLP-1 peptide, as previously described. In some embodiments, the GLP-1 RA is a dual-receptor agonist that binds to the GLP-1 receptor and an additional receptor. The additional receptor can any of the following receptors: a glucagon receptor, a GIP receptor, a cholecystokinin receptor, a xenin receptor, a secretin receptor, a neuropeptide Y receptor, or a neurotensin receptor. For instance, the GLP- 1 RA can be a dual GLP-1 / glucagon receptor agonist that binds to the GLP-1 receptor and the glucagon receptor. Examples of dual GLP-1 / glucagon receptor agonists include efinopegdutide, cotadutide, mazdutide, and BI 45690. In such embodiments, the peptide of the dual GLP-1 / glucagon receptor agonist can be an analogue of oxyntomodulin, which is a gut hormone that activates both the GLP-1 receptor and the glucagon receptor. As another example, the GLP-1 RA can be a dual GLP-1 / GIP receptor agonist that binds to the GLP-1 receptor and the GIP receptor. Examples of dual GLP-1 / GIP receptor agonists include tirzepatide, LY3493269, VK2735, CT-868, and AMG133. In such embodiments, the peptide of the dual GLP-1 / GIP receptor agonist can be an analogue of GIP, which has high sequence similarity to GLP-1 in the N-terminal part of the peptide. In some embodiments, the GLP-1 RA is a triple-receptor agonist that binds to the GLP-1 receptor and two additional receptors. The additional receptors can be any two of the following receptors: a glucagon receptor, a GIP receptor, a cholecystokinin receptor, a xenin receptor, a secretin receptor, a neuropeptide Y receptor, or a neurotensin receptor. For Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO example, the GLP-1RA can be a triple GLP-1 / glucagon / GIP receptor agonist that binds to the GLP-1 receptor, the glucagon receptor, and the GIP receptor. Examples of triple GLP- 1 / glucagon / GIP receptor agonists include retatrutide. The peptide of the GLP-1 RA can be attached to at least one substituent (also referred to herein as a “side chain”). The substituent can prolong the half-life of the peptide in vivo, such as by binding of the substituent to serum albumin. Optionally, the substituent can provide other beneficial effects, such as enhancing solubility, promoting cellular uptake, and / or reducing immunogenicity. The substituent of the GLP-1 RA can be attached to the peptide of the GLP-1 RA via any suitable mechanism, such as acylation, alkylation, ester formation, amide formation, coupling to a cysteine residue, and / or other conjugation chemistries known to those of skill in the art. For example, the substituent can be covalently attached to the peptide via an amide bond between a carboxyl group of the substituent and an amino group of the peptide. The amino group of the peptide can be the N-terminal amino group of the peptide or can be a side chain amino group of an amino acid residue of the peptide (e.g., an amino group of a lysine residue of the peptide). The substituent can be attached to the peptide directly, or can be attached to the peptide indirectly via a linker, which may also be referred to herein as a spacer. For instance, the substituent can be attached to the peptide via an amide bond between a carboxyl group of the linker and an amino group of an amino acid residue of the peptide. The linker can be any suitable linker known to those of skill in the art, such as a peptide linker (e.g., a Ȗ-glutamate linker), a hydrophilic spacer (e.g., 8-amino-3,6-dioxaoctanoic acid), a hydrophobic spacer, or combination thereof. For example, the GLP-1 RA can be an acylated peptide that is attached to a lipophilic substituent having a plurality of carbon atoms, such as at least 10, 15, 20, 25, 30, 35, or 40 carbon atoms. In some embodiments, the lipophilic substituent is an acyl group of a fatty acid, such as a straight chain fatty acid or a branched fatty acid. The fatty acid can be a fatty monoacid, e.g., an aliphatic monocarboxylic acid having 4 to 38 carbon atoms, which may be saturated or unsaturated. The fatty acid can be a fatty diacid, e.g., an aliphatic dicarboxylic acid having 4 to 38 carbon atoms, which may be saturated or unsaturated. The fatty acid can be a C4 to C38 fatty acid, such as a C4 fatty acid, a C6 fatty acid, a C8 fatty acid, a C10 fatty acid, a C12 fatty acid, a C14 fatty acid, a C15 fatty acid, a C16 fatty acid, a C17 fatty acid, a C18 Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO fatty acid, a C20 fatty acid, a C22 fatty acid, a C24 fatty acid, a C26 fatty acid, a C28 fatty acid, a C30 fatty acid, a C32 fatty acid, a C34 fatty acid, a C36 fatty acid, or a C38 fatty acid. In some embodiments, the lipophilic substituent is an acyl group having the formula CH3(CH2)nCO–, where n is an integer from 4 to 38, or from 4 to 24, such as CH3(CH2)4CO–, CH3(CH2)6CO–, CH3(CH2)8CO–, CH3(CH2)10CO–, CH3(CH2)12CO–, CH3(CH2)14CO–, CH3(CH2)16CO–, CH3(CH2)18CO–, CH3(CH2)20CO–, CH3(CH2)22CO–, or CH3(CH2)24CO–. In some embodiments, the lipophilic substituent is an acyl group having the formula HOOC(CH2)nCO–, where n is an integer from 4 to 38, or from 4 to 24, such as HOOC(CH2)14CO–, HOOC(CH2)16CO–, HOOC(CH2)18CO–, HOOC(CH2)20CO–, or HOOC(CH2)22CO–. In some embodiments, the lipophilic substituent is an acyl group of a straight- chain or branched alkane Į,^-dicarboxylic acid. In some embodiments, the lipophilic substituent is an acyl group having the formula HOOC(CH2)nCO–, where n is an integer from 4 to 38, or from 4 to 24, such as HOOC(CH2)16CO–, HOOC(CH2)18CO–, HOOC(CH2)20CO–, or HOOC(CH2)22CO. In some embodiments, the lipophilic substituent is an acyl group having the formula CH3(CH2)nCO–NHCH(COOH)(CH2)2CO–, where n is an integer from 10 to 24. In some embodiments, the lipophilic substituent is an acyl group having the formula CH3(CH2)nCO–NHCH((CH2)2COOH)CO–, where n is an integer from 8 to 24. In some embodiments, the lipophilic substituent is an acyl group having the formula COOH(CH2)nCO–, where n is an integer from 8 to 24. In some embodiments, the lipophilic substituent is an acyl group having the formula –NHCH(COOH)(CH2)4NH–CO(CH2)nCH3, where n is an integer from 8 to 18. The lipophilic substituent can be attached to the peptide of the GLP-1 RA via a linker, as described herein. In some embodiments, the lipophilic substituent interacts with a component of the dynamic hydrogel to promote encapsulation and controlled release of the GLP-1 RA from the dynamic hydrogels, as described further below. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO In some embodiments, a composition of the present technology includes a dynamic hydrogel and an incretin mimetic encapsulated by the dynamic hydrogel. The incretin mimetic can be a GLP-1 RA, such as one or more of exenatide, exenatide-LAR, lixisenatide, liraglutide, semaglutide, albiglutide, dulaglutide, efpeglenatide, ecnoglutide, efinopegdutide, cotadutide, mazdutide, BI 45690, tirzepatide, LY3493269, VK2735, CT-868, AMG133, or retatrutide. In some embodiments, the incretin mimetic is a GLP-1 RA that is an acylated peptide, such as one or more of liraglutide, semaglutide, ecnoglutide, cotadutide, mazdutide, tirzepatide, or retatrutide. Additional examples of GLP-1 RAs and incretin mimetics are provided in International Publication Nos. WO 2005 / 027978 and WO 2014 / 005858, the disclosures of each of which are incorporated by reference herein in their entirety. Optionally, the composition can include a combination of two or more different incretin mimetics, such as two or more of any of the incretin mimetics disclosed herein. Optionally, the compositions herein can include other therapeutic cargo carried by the dynamic hydrogel, in addition to the incretin mimetic. The other therapeutic cargo can include one or more therapeutic agents that produce a desired therapeutic effect, such as small molecule drugs, peptides, proteins, polysaccharides, nucleic acids, cells, or combinations thereof. In some embodiments, the therapeutic agent(s) act in concert with the incretin mimetic to treat the disease or condition, such as antidiabetic agents, antiobesity agents, appetite suppressants, and / or antihypertensive agents. Examples of such therapeutic agents include alpha-glucosidase inhibitors, amylin analogues (e.g., cagrilintide), biguanides, DPP4- inhibitors, glucagon antagonists, insulin and insulin analogues (e.g., insulin degludec, insulin detemir, insulin icodec, insulin glargine), meglitinides, SGLT-2 inhibitors, sulfonylureas, thiazolidinediones, and combinations thereof. Such therapeutic agents can be encapsulated in the dynamic hydrogel via physical entrapment, interactions with hydrogel components (e.g., hydrophobic interactions), or suitable combinations thereof. For instance, therapeutic agents that precipitate at physiological pH (e.g., insulin glargine) can be physically entrapped within the hydrogel. Optionally, the therapeutic agent(s) can be administered to the subject separately from the incretin mimetic via any suitable administration route (e.g., parenteral or non- parenteral administration). Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 2. Acylated Peptides Although certain embodiments of the compositions herein are described in connection with incretin mimetics such as GLP-1 RAs, this is not intended to be limiting, and the compositions of the present technology can be used to deliver other types of therapeutic peptides, such as acylated peptides. Acylation of peptides with a lipophilic substituent (e.g., a fatty acid moiety) can produce improved pharmacokinetics compared to the native peptide via binding to serum albumin, while maintaining the activity of the native peptide. Other beneficial effects of acylation can include enhancing solubility, promoting cellular uptake, and / or reducing immunogenicity. In some embodiments, a composition of the present technology includes a dynamic hydrogel and at least one acylated peptide encapsulated by the dynamic hydrogel. The acylated peptide can include a peptide that exhibits a therapeutic effect when administered to the subject, and at least one substituent that is attached to the peptide via acylation. The peptide can be a native peptide (e.g., having 100% sequence identity to the sequence of the endogenous human peptide), or can be an analogue with one or more modifications relative to the native peptide (e.g., having less than 100% sequence identity to the sequence of the endogenous human peptide). For instance, the native peptide sequence can be modified by substitution of one or more amino acids (e.g., with a natural or non-natural amino acid), addition of one or more amino acids (e.g., a natural or non-natural amino acid), deletion of one or more amino acids, or suitable combinations thereof. The peptide can be produced in suitable host cells via recombinant DNA technology, can be produced in a cell-free system, or can be produced synthetically via solid phase synthesis. The lipophilic substituent of the acylated peptide can have a plurality of carbon atoms, such as at least 10, 15, 20, 25, 30, 35, or 40 carbon atoms. In some embodiments, the lipophilic substituent is an acyl group of a fatty acid, such as a straight chain fatty acid or a branched fatty acid. The fatty acid can be a fatty monoacid, e.g., an aliphatic monocarboxylic acid having 4 to 38 carbon atoms, which may be saturated or unsaturated. The fatty acid can be a fatty diacid, e.g., an aliphatic dicarboxylic acid having 4 to 38 carbon atoms, which may be saturated or unsaturated. The fatty acid can be a C4 to C38 fatty acid, such as a C4 fatty acid, a C6 fatty acid, a C8 fatty acid, a C10 fatty acid, a C12 fatty acid, a C14 fatty acid, a C15 fatty acid, a C16 fatty acid, a C17 fatty acid, a C18 fatty acid, a C20 fatty acid, a C22 fatty acid, Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO a C24 fatty acid, a C26 fatty acid, a C28 fatty acid, a C30 fatty acid, a C32 fatty acid, a C34 fatty acid, a C36 fatty acid, or a C38 fatty acid. In some embodiments, the lipophilic substituent is an acyl group having the formula CH3(CH2)nCO–, where n is an integer from 4 to 38, or from 4 to 24, such as CH3(CH2)4CO–, CH3(CH2)6CO–, CH3(CH2)8CO–, CH3(CH2)10CO–, CH3(CH2)12CO–, CH3(CH2)14CO–, CH3(CH2)16CO–, CH3(CH2)18CO–, CH3(CH2)20CO–, CH3(CH2)22CO–, or CH3(CH2)24CO–. In some embodiments, the lipophilic substituent is an acyl group having the formula HOOC(CH2)nCO–, where n is an integer from 4 to 38, or from 4 to 24, such as HOOC(CH2)14CO–, HOOC(CH2)16CO–, HOOC(CH2)18CO–, HOOC(CH2)20CO–, or HOOC(CH2)22CO–. In some embodiments, the lipophilic substituent is an acyl group of a straight- chain or branched alkane Į,^-dicarboxylic acid. In some embodiments, the lipophilic substituent is an acyl group having the formula HOOC(CH2)nCO–, where n is an integer from 4 to 38, or from 4 to 24, such as HOOC(CH2)16CO–, HOOC(CH2)18CO–, HOOC(CH2)20CO–, or HOOC(CH2)22CO. In some embodiments, the lipophilic substituent is an acyl group having the formula CH3(CH2)nCO–NHCH(COOH)(CH2)2CO–, where n is an integer from 10 to 24. In some embodiments, the lipophilic substituent is an acyl group having the formula CH3(CH2)nCO–NHCH((CH2)2COOH)CO–, where n is an integer from 8 to 24. In some embodiments, the lipophilic substituent is an acyl group having the formula COOH(CH2)nCO–, where n is an integer from 8 to 24. In some embodiments, the lipophilic substituent is an acyl group having the formula –NHCH(COOH)(CH2)4NH–CO(CH2)nCH3, where n is an integer from 8 to 18. In some embodiments, the lipophilic substituent interacts with a component of the dynamic hydrogel to promote encapsulation and controlled release of the acylated peptide from the dynamic hydrogels, as described further below. In some embodiments, the lipophilic substituent is covalently attached to the peptide via an amide bond between a carboxyl group of the substituent and an amino group of Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO the peptide. The amino group of the peptide can be the N-terminal amino group of the peptide or a side chain amino group of an amino acid residue of the peptide (e.g., an amino group of a lysine residue). The lipophilic substituent can be attached to the peptide directly, or can be attached to the peptide indirectly via a linker. For instance, the lipophilic substituent can be attached to the peptide via an amide bond between a carboxyl group of the linker and an amino group of an amino acid residue of the peptide. The linker can be any suitable linker known to those of skill in the art, such as a peptide linker (e.g., an amino acid, a Ȗ-glutamate linker), a hydrophilic spacer (e.g., PEG, 8-amino-3,6-dioxaoctanoic acid (OEG)), a hydrophobic spacer, or combination thereof. In some embodiments, the acylated peptide is an acylated analogue of a proglucagon-derived peptide. Proglucagon-derived peptides are a family of peptides that are derived from differential processing of a common prohormone, proglucagon, and include glucagon, GLP-1, glucagon-like peptide-2 (GLP-2), oxyntomodulin (OXM), glicentin, glicentin-related pancreatic peptide (GRPP), intervening peptide-1 (IP-1), intervening peptide- 2 (IP-2), and major proglucagon fragment (MPGF). These peptides exhibit a wide variety of physiological effects, including metabolism, energy regulation, cardioprotection, bone health, renal function, liver function, and cognition. The acylated analogue of the proglucagon peptide can include a peptide including a sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99%, or 100% sequence identity to the native proglucagon peptide, and a lipophilic substituent attached to the peptide, as described herein. In some embodiments, the acylated peptide is an acylated amylin analogue, such as cagrilintide. Amylin is a hormone that is secreted by pancreatic ȕ-cells in response to nutrient ingestion. Amylin signaling plays a role in the regulation of blood glucose by delaying gastric emptying, suppressing food intake, and inhibiting meal-related glucagon secretion, and is thus complementary to the activity of the incretin hormones. The acylated amylin analogue can include a peptide including a sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99%, or 100% sequence identity to the native amylin peptide, and a lipophilic substituent attached to the peptide, as described herein. In some embodiments, the acylated peptide is an acylated insulin analogue, such as insulin degludec, insulin detemir, or insulin icodec. An acylated insulin analogue can be codelivered with an incretin mimetic for treatment of diabetes. The acylated insulin analogue Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO can include a peptide including a sequence having at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99%, or 100% sequence identity to the native insulin peptide, and a lipophilic substituent attached to the peptide, as described herein. B. Compositions and Methods In some embodiments, the present technology provides compositions including a dynamic hydrogel and one or more therapeutic peptides (e.g., an incretin mimetic and / or acylated peptide) encapsulated by the dynamic hydrogel. The dynamic hydrogel carrying the therapeutic peptide can be any of the dynamic hydrogels described in Section I above. For example, the dynamic hydrogel can be a PNP hydrogel composed of a polymer and a plurality of nanoparticles that interact non-covalently with each other, as previously discussed in Section I.A. The dynamic hydrogel can exhibit shear-thinning, self-healing, and / or viscoelastic properties resulting from non-covalent, supramolecular interactions between the hydrogel components, as described above in Section I.B. The composition can include any suitable amount of the therapeutic peptide for providing the desired therapeutic effect. For example, the composition can include at least 1 mg, 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, or 400 mg of the therapeutic peptide. Alternatively or in combination, the composition can include no more than 500 mg, 400 mg, 300 mg, 275 mg, 250 mg, 225 mg, 200 mg, 175 mg, 150 mg, 125 mg, 100 mg, 90 mg, 80 mg, 70 mg, 60 mg, 50 mg, 45 mg, 40 mg, 35 mg, 30 mg, 25 mg, 20 mg, 15 mg, 10 mg, 5 mg, or 2 mg of the therapeutic peptide. The amount of the therapeutic peptide in the composition can be within a range from 1 mg to 500 mg, 1 mg to 250 mg, 1 mg to 150 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 40 mg, 1 mg to 30 mg, 1 mg to 20 mg, 1 mg to 10 mg, 10 mg to 500 mg, 10 mg to 250 mg, 10 mg to 150 mg, 10 mg to 100 mg, 10 mg to 50 mg, 10 mg to 40 mg, 10 mg to 30 mg, 10 mg to 20 mg, 20 mg to 500 mg, 20 mg to 250 mg, 20 mg to 150 mg, 20 mg to 100 mg, 20 mg to 50 mg, 20 mg to 40 mg, 20 mg to 30 mg, 30 mg to 500 mg, 30 mg to 250 mg, 30 mg to 150 mg, 30 mg to 100 mg, 30 mg to 50 mg, 30 mg to 40 mg, 40 mg to 500 mg, 40 mg to 250 mg, 40 mg to 150 mg, 40 mg to 100 mg, 40 mg to 50 mg, 50 mg to 500 mg, 50 mg to 250 mg, 50 mg to 150 mg, 50 mg to 100 mg, 100 mg to 500 mg, 100 mg to 250 mg, 100 mg to 150 mg, 150 mg to 500 mg, 150 mg to 250 mg, or 250 mg to 500 mg. The amount of the therapeutic peptide in the composition can be Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO approximately 1 mg, 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 400 mg, or 500 mg. In some embodiments, the therapeutic peptide is present in the composition at a concentration of at least 0.5 mg / mL, 1 mg / mL, 1.5 mg / mL, 2 mg / mL, 5 mg / mL, 10 mg / mL, 20 mg / mL, 50 mg / mL, 100 mg / mL, 120 mg / mL, or 150 mg / mL. Alternatively or in combination, the concentration of the therapeutic peptide in the composition is no more than 200 mg / mL, 150 mg / mL, 120 mg / mL, 100 mg / mL, 50 mg / mL, 20 mg / mL, 10 mg / mL, 5 mg / mL, 2 mg / mL, 1.5 mg / mL, 1 mg / mL, or 0.5 mg / mL. The concentration of the therapeutic peptide in the composition can be within a range from 0.5 mg / mL to 200 mg / mL, 0.5 mg / mL to 150 mg / mL, 0.5 mg / mL to 120 mg / mL, 0.5 mg / mL to 100 mg / mL, 0.5 mg / mL to 50 mg / mL, 0.5 mg / mL to 20 mg / mL, 0.5 mg / mL to 10 mg / mL, 0.5 mg / mL to 5 mg / mL, 0.5 mg / mL to 2 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 0.5 mg / mL to 1 mg / mL, 1 mg / mL to 200 mg / mL, 1 mg / mL to 150 mg / mL, 1 mg / mL to 120 mg / mL, 1 mg / mL to 100 mg / mL, 1 mg / mL to 50 mg / mL, 1 mg / mL to 20 mg / mL, 1 mg / mL to 10 mg / mL, 1 mg / mL to 50 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 1 mg / mL to 1.5 mg / mL, 1.5 mg / mL to 200 mg / mL, 1.5 mg / mL to 150 mg / mL, 1.5 mg / mL to 120 mg / mL, 1.5 mg / mL to 100 mg / mL, 1.5 mg / mL to 50 mg / mL, 1.5 mg / mL to 20 mg / mL, 1.5 mg / mL to 10 mg / mL, 1.5 mg / mL to 5 mg / mL, 1.5 mg / mL to 2 mg / mL, 2 mg / mL to 200 mg / mL, 2 mg / mL to 150 mg / mL, 2 mg / mL to 120 mg / mL, 2 mg / mL to 100 mg / mL, 2 mg / mL to 50 mg / mL, 2 mg / mL to 20 mg / mL, 2 mg / mL to 10 mg / mL, 2 mg / mL to 5 mg / mL, 5 mg / mL to 200 mg / mL, 5 mg / mL to 150 mg / mL, 5 mg / mL to 120 mg / mL, 5 mg / mL to 100 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 20 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 200 mg / mL, 10 mg / mL to 150 mg / mL, 10 mg / mL to 120 mg / mL, 10 mg / mL to 100 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 20 mg / mL, 20 mg / mL to 200 mg / mL, 20 mg / mL to 150 mg / mL, 20 mg / mL to 120 mg / mL, 20 mg / mL to 100 mg / mL, 20 mg / mL to 50 mg / mL, 50 mg / mL to 200 mg / mL, 50 mg / mL to 150 mg / mL, 50 mg / mL to 120 mg / mL, 50 mg / mL to 100 mg / mL, or 100 mg / mL to 200 mg / mL. In some embodiments, the size of the therapeutic peptide is smaller than the mesh size of the dynamic hydrogel. For example, the mesh size of the dynamic hydrogel can be greater than or equal to 2 nm, 2.5 nm, 3 nm, 3.5 nm, 4 nm, 4.5 nm, or 5 nm; while the size of the therapeutic peptide (e.g., hydrodynamic diameter) can be less than 2 nm, 1.5 nm, 1 nm, Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO or 0.5 nm. Accordingly, physical entrapment of the therapeutic peptide by the hydrogel network may be ineffective for producing controlled release, in that the therapeutic peptide may be able to diffuse freely out of the dynamic hydrogel, resulting in uncontrolled burst release in vivo. For example, physical entrapment may be insufficient for controlling the release of a therapeutic peptide having a molecular weight less than or equal to 5 kDa, 4.5 kDa, 4 kDa, or 3.5 kDa. In such embodiments, the dynamic hydrogel can include at least one component that binds to the therapeutic peptide to control the release of the therapeutic peptide from the dynamic hydrogel. The interaction can be a non-covalent interaction, such as a hydrophobic interaction. For instance, in embodiments where the therapeutic peptide is acylated with a fatty acid, the lipid in the fatty acid can interact with one or more hydrophobic components of the dynamic hydrogel (e.g., for a PNP hydrogel, the hydrophobic surfaces of the nanoparticles and / or hydrophobic moieties on the polymer chain). These hydrophobic interactions can cause the therapeutic peptide to adhere to the hydrophobic components of the dynamic hydrogel, thus inhibiting uncontrolled diffusion of the therapeutic peptide out of the dynamic hydrogel. In such embodiments, the therapeutic peptide can be released from the dynamic hydrogel primarily or entirely via erosion of the dynamic hydrogel in vivo. The release kinetics of the therapeutic peptide can thus be adjusted by tuning the degradation rate of the dynamic hydrogel (e.g., by controlling the storage modulus of the dynamic hydrogel). In some instances, therapeutic peptides may exhibit aggregation behavior that may interfere with binding of the therapeutic peptide to the dynamic hydrogel, thus resulting in a significant fraction of “free” peptide that is released diffusively over undesirably short timeframes from the hydrogel. For example, semaglutide has been shown to form a dimer species. When dimerized, the fatty acid side chain of semaglutide may be unavailable for hydrophobic interactions with the hydrogel, but the semaglutide dimers may still be too small for physical entrapment by the hydrogel network. Thus, when administered in vivo, the semaglutide may be rapidly released over a short timeframe, resulting in excessively high Cmax values that may produce undesirable gastrointestinal side effects. Accordingly, the compositions herein can include at least one dispersing agent that inhibits aggregation of the therapeutic peptide (e.g., by weakening or otherwise disrupting interactions of the therapeutic peptide with other therapeutic peptides) in order to enhance Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO binding of the therapeutic peptide to the dynamic hydrogel. For example, the dispersing agent can include one or more surfactants, such as a nonionic surfactant, an anionic surfactant, a cationic surfactant and / or a zwitterionic surfactant. Examples of surfactants that may be used include polysorbates (e.g., polysorbate 20 (Tween-20), polysorbate 40 (Tween-40), polysorbate 60 (Tween-60), polysorbate 80 (Tween-80)), sorbitan fatty acid esters (e.g., sorbitan monolaurate (Span 20), sorbitan monostearate (Span 60), sorbitan tristearate (Span 65)), poloxamers (e.g., P188, P237, P338, P407), polyoxyethylene alkyl ethers (e.g., Brij surfactants), alkyl sulfates (e.g., dodecyl sulfate) and salts thereof (e.g., sodium dodecyl sulfate (SDS)), fatty acids (e.g., lauric acid, myristic acid, palmitic acid, stearic acid), fatty alcohols (e.g., lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol), phospholipids, and other lipids or derivatives thereof exhibiting surfactant behavior. As another example, the dispersing agent can include one or more tonicity agents, such as alcohol-related tonicity agents (e.g., propylene glycol, glycerol, mannitol). Optionally, the compositions herein can include a combination of two or more dispersing agents, such as a surfactant and a tonicity agent (e.g., Tween-20 and polysorbate). The dispersing agent(s) can be mixed with the therapeutic peptide before the therapeutic peptide is combined with the components of the dynamic hydrogel. In some embodiments, the concentration of the dispersing agent is sufficiently to inhibit aggregation of the therapeutic peptide, but sufficiently low to avoid interfering with the interactions between the therapeutic peptide and the dynamic hydrogel, and / or to avoid interfering with hydrogel formation. For example, the concentration of the dispersing agent in the composition can be no more than 50 mg / mL, 40 mg / mL, 30 mg / mL, 25 mg / mL, 20 mg / mL, 15 mg / mL, 10 mg / mL, 5 mg / mL, 4 mg / mL, 3 mg / mL, 2 mg / mL, 1.5 mg / mL, 1 mg / mL, or 0.5 mg / mL. The concentration of the dispersing agent in the composition can be within a range from 0.5 mg / mL to 50 mg / mL, 0.5 mg / mL to 25 mg / mL, 0.5 mg / mL to 15 mg / mL, 0.5 mg / mL to 10 mg / mL, 0.5 mg / mL to 5 mg / mL, 0.5 mg / mL to 2 mg / mL, 0.5 mg / mL to 1 mg / mL, 1 mg / mL to 50 mg / mL, 1 mg / mL to 25 mg / mL, 1 mg / mL to 15 mg / mL, 1 mg / mL to 10 mg / mL, 1 mg / mL to 5 mg / mL, 1 mg / mL to 2 mg / mL, 2 mg / mL to 50 mg / mL, 2 mg / mL to 25 mg / mL, 2 mg / mL to 15 mg / mL, 2 mg / mL to 10 mg / mL, 2 mg / mL to 5 mg / mL, 5 mg / mL to 50 mg / mL, 5 mg / mL to 25 mg / mL, 5 mg / mL to 15 mg / mL, 5 mg / mL to 10 mg / mL, 10 mg / mL to 50 mg / mL, 10 mg / mL to 25 mg / mL, 10 mg / mL to 15 mg / mL, 15 mg / mL to 50 mg / mL, 15 mg / mL to 25 mg / mL, or 25 mg / mL to 50 mg / mL. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO The concentration of the dispersing agent in the composition can depend on the type of dispersing agent used. For instance, in embodiments where the dispersing agent is or includes a surfactant (e.g., Tween-20), the surfactant can be present in the composition at a concentration less than or equal to 5 mg / mL, 4 mg / mL, 3 mg / mL, 2 mg / mL, 1.5 mg / mL, 1.2 mg / mL, 1.1 mg / mL, 1 mg / mL, or 0.5 mg / mL. The concentration of the surfactant can be within a range from 0.1 mg / mL to 5 mg / mL, 0.5 mg / mL to 1.5 mg / mL, or 1 mg / mL to 2 mg / mL. As another example, in embodiments where the dispersing agent is or includes a tonicity agent (e.g., propylene glycol), the tonicity agent can present in the composition within a range from 1 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, or 16 mg / mL to 26 mg / mL. In some embodiments, the compositions herein include little or no saline. Saline can increase hydrophobic effects that promote aggregation of the therapeutic peptide. Accordingly, removal of saline from the therapeutic peptide solution can reduce aggregation and enhance binding of the therapeutic peptide to the dynamic hydrogel. In some embodiments, the concentration of sodium chloride in the composition is no more than 5 mg / mL, 4 mg / mL, 3 mg / mL, 2 mg / mL, 1.5 mg / mL, 1 mg / mL, 0.5 mg / mL, 0.25 mg / mL, 0.1 mg / mL, 0.05 mg / mL, or 0.01 mg / mL. In some embodiments, the compositions herein do not include any sodium chloride. In other embodiments, however, the size of the therapeutic peptide can be larger than the mesh size of the dynamic hydrogel, such as if the therapeutic peptide is conjugated to, binds to, or otherwise attached to a larger molecule or component (e.g., a protein or microparticle), and / or if the therapeutic peptide precipitates under formulation conditions to form larger aggregates. For example, albiglutide and dulaglutide are conjugated to proteins or protein fragments, and exenatide-LAR is encapsulated in biodegradable microparticles. In such embodiments, the therapeutic peptide can be encapsulated in the dynamic hydrogel via physical entrapment by the hydrogel network. In embodiments where the therapeutic peptide includes a lipophilic substituent (e.g., a fatty acid side chain), the composition can further include a binding agent that binds to and / or otherwise interacts with the lipophilic substituent (e.g., via non-covalent interactions such as hydrophobic interactions). For example, the binding agent can be albumin. The binding agent can be sufficiently large to be physically entrapped within the hydrogel network of the Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO dynamic hydrogel. Accordingly, when the larger molecule is present in the composition, the therapeutic peptide can be bound to the binding agent via interactions between the lipophilic substituent and the binding agent, and thus be physically entrapped within the dynamic hydrogel along with the binding agent. In some embodiments, the binding agent is present in the composition in an amount within a range from 0.1 molar equivalents to 1 molar equivalents relative to the amount of the therapeutic peptide in the composition. In some embodiments, there is at least 1 molar equivalent of the therapeutic peptide per binding site on the binding agent (e.g., albumin has two binding sites for lipophilic substituents). The binding agent may be used in combination with a dispersing agent or without a dispersing agent. The compositions herein can be administered to the subject via any suitable route, such as a parenteral route. For example, in some embodiments, the composition is administered to the subject via injection (e.g., subcutaneous injection or intramuscular injection). The shear-thinning properties of the dynamic hydrogel can allow for delivery via injection, while the self-healing properties of the dynamic hydrogel can allow for formation of a depot at the injection site that produces controlled release of the therapeutic peptide over the desired treatment period. Injection of the composition can be performed using any suitable tubular device having a lumen configured for delivery of a hydrogel, such as needles (e.g., hypodermic needles, surgical needles, infusion needles), injector pens, catheters, trocars, cannulas, tubing, etc. The composition can be injected into any suitable site in the subject’s body, such as an arm, thigh, abdomen, or buttock. The composition can be formulated to have a volume that is sufficiently small for injection, such as a volume less than or equal to 2 mL, 1.75 mL, 1.5 mL, 1.25 mL, 1 mL, 0.75 mL, 0.5 mL, or 0.25 mL. In some embodiments, the composition is administered as a single injection at a single injection site, while in other embodiments, the composition can be administered as multiple injections at the same or different injection sites. The composition can be administered to the subject at any suitable frequency, such as once per week, once per 2 weeks, once per 4 weeks, once per month, once per 2 months, once per 3 months, once per 4 months, once per 5 months, once per 6 months, once 9 months, or once per year. The compositions herein can be configured to deliver a therapeutically effective amount of the therapeutic peptide over a desired treatment period, which can be an amount that is effective to ameliorate or prevent a symptom of a disease or condition in a subject. For Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO example, the treatment period can be at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 28 days, 35 days, 40 days, 50 days, 60 days, 70 days, 80 days, 90 days, 100 days, 110 days, 120 days, 150 days, 180 days, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or 1 year. The treatment period can be approximately 2 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 9 months, or 12 months. The treatment period can be modulated by tuning the degradation rate of the hydrogel, as described elsewhere herein. During the treatment period, the composition can deliver the therapeutic peptide at a rate of approximately 0.1 mg / week, 0.25 mg / week, 0.5 mg / week, 1 mg / week, 1.5 mg / week, 2 mg / week, 2.5 mg / week, 3 mg / week, 4 mg / week, 5 mg / week, 6 mg / week, 7 mg / week, 8 mg / week, 9 mg / week, 10 mg / week, 11 mg / week, 12 mg / week, 15 mg / week, 20 mg / week, or 25 mg / week. The delivery rate can be within a range from 0.1 mg / week to 25 mg / week, 0.25 mg / week to 25 mg / week, 0.5 mg / week to 20 mg / week, 0.5 mg / week to 2 mg / week, 0.5 mg / week to 1.5 mg / week, 1 mg / week to 2 mg / week, 2 mg / week to 5 mg / week, 5 mg / week to 15 mg / week, 5 mg / week to 10 mg / week, 10 mg / week to 20 mg / week, 10 mg / week to 15 mg / week, 12 mg / week to 25 mg / week, 12 mg / week to 15 mg / week, 15 mg / week to 25 mg / week, 15 mg / week to 20 mg / week, or 20 mg / week to 25 mg / week. Alternatively or in combination, the composition can deliver the therapeutic peptide at a rate of approximately 0.5 wt% / day, 0.6 wt% / day, 0.7 wt% / day, 0.8 wt% / day, 0.9 wt% / day, 1 wt% / day, 1.25 wt% / day, 1.5 wt% / day, 1.75 wt% / day, 2 wt% / day, 2.5 wt% / day, 3 wt% / day, 4 wt% / day, or 5 wt% / day (the wt% of the GLP-1 RA can be measured relative to the total amount of the therapeutic peptide initially present in the composition). In some embodiments, when administered to a subject in vivo, the composition produces a steady state concentration (Csteady-state) and / or mean concentration at steady state of the therapeutic peptide in serum of approximately 10 ng / mL, 25 ng / mL, 50 ng / mL, 75 ng / mL, 100 ng / mL, 150 ng / mL, 200 ng / mL, 250 ng / mL, 300 ng / mL, 350 ng / mL, 400 ng / mL, 500 ng / mL, 600 ng / mL, 700 ng / mL, 800 ng / mL, 900 ng / mL, 1000 ng / mL, 1500 ng / mL, or 2000 ng / mL. The Csteady-state of the therapeutic peptide in serum produced by the composition can be within a range from 10 ng / mL to 2000 ng / mL, 10 ng / mL to 1000 ng / mL, 10 ng / mL to 500 ng / mL, 10 ng / mL to 100 ng / ml, 10 ng / mL to 50 ng / mL, 10 ng / mL to 25 ng / mL, 50 ng / mL to 2000 ng / mL, 50 ng / mL to 1000 ng / ml, 50 ng / mL to 500 ng / mL, 50 ng / mL, to 100 ng / mL, 100 Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO ng / mL to 2000 ng / mL, 100 ng / mL to 1000 ng / mL, 100 ng / mL to 500 ng / mL, 100 ng / mL to 300 ng / mL, 150 ng / mL to 250 ng / mL, 500 ng / mL to 2000 ng / mL, 500 ng / mL to 1000 ng / mL, or 1000 ng / ml to 2000 ng / mL. The Csteady-state of the therapeutic peptide can be achieved within the first 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days of administering the composition to the subject. In some embodiments, when administered to a subject in vivo, the composition produces a maximum concentration (Cmax) of the therapeutic peptide in serum that is less than or equal to 2000 ng / mL, 1500 ng / mL, 1000 ng / mL, or 500 ng / mL. In some embodiments, when administered to a subject in vivo, the composition produces a Cmaxof the therapeutic peptide in serum that is no more than 1000X, 500X, 200X, 100X, 50X, or 10X of the Csteady-stateand / or mean concentration at steady state of the therapeutic peptide in serum. In some embodiments, the present technology provides methods for treating a subject by administering a composition as described herein. The composition can treat a disease or condition of the subject by producing a desired therapeutic effect in the subject, such as alleviation of symptoms, a reduction in the severity of the disease or condition, inhibiting an underlying cause of the disease or condition, steadying the disease or condition in a non- advanced state, delaying the progress of a disease or condition, and / or improvement or alleviation of the disease or condition. Examples of diseases and conditions that may be treated using the compositions described herein include diabetes and / or related conditions (e.g., prediabetes, type 1 diabetes, type 2 diabetes, hyperglycemia, impaired glucose tolerance), obesity or excessive body weight, eating disorders (e.g., bulimia nervosa, binge eating disorder), obstructive sleep apnea, cardiovascular disease (e.g., hypertension, atherosclerosis, myocardial infarction, coronary heart diseases), liver disease (e.g., non-alcoholic fatty liver disease), neurological and / or neurodegenerative diseases (e.g., Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, peripheral neuropathy, ischemia, stroke, multiple sclerosis), inflammatory diseases (e.g., asthma, psoriasis, inflammatory bowel disease), renal diseases, bone diseases (e.g., bone fragility, osteoporosis), hormonal diseases (e.g., polycystic ovary syndrome), and gastrointestinal diseases (e.g., short bowel syndrome). In some embodiments, a method of treating diabetes and / or a diabetes-related condition (e.g., prediabetes, type 1 diabetes, type 2 diabetes, hyperglycemia, impaired glucose tolerance) includes administering a composition of the present technology to a subject in need thereof. The composition can be administered to the subject via a single injection (e.g., a Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO subcutaneous or intramuscular injection). The composition can include a dynamic hydrogel (e.g., a PNP hydrogel) encapsulating a therapeutically effective amount of a therapeutic peptide (e.g., an incretin mimetic such as a GLP-1 RA) for treating the diabetes and / or diabetes-related condition. For example, the therapeutically effective amount can be an amount of the therapeutic peptide that results in the sustained reduction and / or regulation of the subject’s blood glucose levels over the treatment period. The therapeutically effective amount can be within a range from 0.1 mg / week to 25 mg / week, 0.1 mg / week to 5 mg / week, 0.5 mg / week to 20 mg / week, 0.5 mg / week to 2 mg / week, 0.75 mg / week to 1.5 mg / week, 1 mg / week to 2 mg / week, 5 mg / week to 10 mg / week, 10 mg / week to 20 mg / week, or 10 mg / week to 15 mg / week. The therapeutically effective amount may vary depending on the type of therapeutic peptide, e.g., the therapeutically effectively amount may be approximately 1 mg / week for semaglutide; approximately 12.6 mg / week (1.8 mg / day) for liraglutide; approximately 2.5 mg / week, 5 mg / week, 7.5 mg / week, 10 mg / week, 12.5 mg / week, or 15 mg / week for tirzepatide; and approximately 1 mg / week, 4 mg / week, 8 mg / week or 12 mg / week for retatrutide. The components of the dynamic hydrogel can be selected to provide injectability, formation of a cohesive depot in vivo, and controlled release of the therapeutic peptide over a sufficiently long period for treatment of the diabetes and / or diabetes-related condition. For example, the treatment period can be at least 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 9 months, or 12 months. For example, the dynamic hydrogel can be a PNP hydrogel (e.g., composed of a hydrophobically modified cellulosic derivative (e.g., HPMC-C12) and a plurality of amphiphilic nanoparticles (e.g., PEG-PLA nanoparticles). The PNP hydrogel can be a 0.5-5 hydrogel, a 0.5-8 hydrogel, a 0.5-10 hydrogel, a 0.5-12 hydrogel, a 0.5-15 hydrogel, a 0.8-5 hydrogel, a 0.8-8 hydrogel, a 0.8-10 hydrogel, a 0.8-12 hydrogel, a 0.8-15 hydrogel, a 1-5 hydrogel, a 1-8 hydrogel, a 1-10 hydrogel, a 1-12 hydrogel, a 1-15 hydrogel, a 1.5-5 hydrogel, a 1.5-8 hydrogel, a 1.5-10 hydrogel, a 1.5-12 hydrogel, a 1.5-15 hydrogel, a 2-5 hydrogel, a 2-8 hydrogel, a 2-10 hydrogel, a 2-12 hydrogel, a 2-15 hydrogel, a 3-5 hydrogel, a 3-8 hydrogel, a 3-10 hydrogel, a 3-12 hydrogel, or a 3-15 hydrogel. Optionally, the dynamic hydrogel can include at least one dispersing agent that inhibits aggregation of the therapeutic peptide, such as a surfactant (e.g., Tween-20) and / or a tonicity agent (e.g., propylene glycol). In some embodiments, a method of treating obesity and / or reducing body weight includes administering a composition of the present technology to a subject in need thereof. The composition can be administered to the subject via a single injection (e.g., a Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO subcutaneous or intramuscular injection). The composition can include a dynamic hydrogel (e.g., a PNP hydrogel) encapsulating a therapeutically effective amount of a therapeutic peptide (e.g., an incretin mimetic such as a GLP-1 RA) for treating obesity and / or reducing body weight of the subject. For example, the therapeutically effective amount can be an amount of the therapeutic peptide that results in loss of a desired amount of body weight and / or maintenance of body weight within a desired range. The therapeutically effective amount can be within a range from 0.1 mg / week to 25 mg / week, 0.1 mg / week to 5 mg / week, 0.5 mg / week to 20 mg / week, 0.5 mg / week to 2 mg / week, 0.75 mg / week to 1.5 mg / week, 1 mg / week to 2 mg / week, 5 mg / week to 10 mg / week, 10 mg / week to 20 mg / week, or 10 mg / week to 15 mg / week. The therapeutically effective amount may vary depending on the type of therapeutic peptide, e.g., the therapeutically effectively amount may be approximately 1 mg / week for semaglutide; approximately 12.6 mg / week (1.8 mg / day) for liraglutide; approximately 2.5 mg / week, 5 mg / week, 7.5 mg / week, 10 mg / week, 12.5 mg / week, or 15 mg / week for tirzepatide; and approximately 1 mg / week, 4 mg / week, 8 mg / week or 12 mg / week for retatrutide. The components of the dynamic hydrogel can be selected to provide injectability, formation of a cohesive depot in vivo, and controlled release of the therapeutic peptide over a sufficiently long period for the treatment of obesity and / or reduction of body weight. For example, the treatment period can be at least 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 9 months, or 12 months. For example, the dynamic hydrogel can be a PNP hydrogel (e.g., composed of a hydrophobically modified cellulosic derivative (e.g., HPMC-C12) and a plurality of amphiphilic nanoparticles (e.g., PEG-PLA nanoparticles). The PNP hydrogel can be a 0.5-5 hydrogel, a 0.5-8 hydrogel, a 0.5-10 hydrogel, a 0.5-12 hydrogel, a 0.5-15 hydrogel, a 0.8-5 hydrogel, a 0.8-8 hydrogel, a 0.8-10 hydrogel, a 0.8-12 hydrogel, a 0.8-15 hydrogel, a 1-5 hydrogel, a 1-8 hydrogel, a 1-10 hydrogel, a 1-12 hydrogel, a 1-15 hydrogel, a 1.5-5 hydrogel, a 1.5-8 hydrogel, a 1.5-10 hydrogel, a 1.5-12 hydrogel, a 1.5-15 hydrogel, a 2-5 hydrogel, a 2- 8 hydrogel, a 2-10 hydrogel, a 2-12 hydrogel, a 2-15 hydrogel, a 3-5 hydrogel, a 3-8 hydrogel, a 3-10 hydrogel, a 3-12 hydrogel, or a 3-15 hydrogel. Optionally, the dynamic hydrogel can include at least one dispersing agent that inhibits aggregation of the therapeutic peptide, such as a surfactant (e.g., Tween-20) and / or a tonicity agent (e.g., propylene glycol). In some embodiments, the present technology provides methods for preparing a composition for treating a disease or condition as described herein. The method can include combining the components of a dynamic hydrogel (e.g., polymer and nanoparticles) with the Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO therapeutic peptide, thus forming a dynamic hydrogel encapsulating the therapeutic peptide. The combining of the hydrogel components and therapeutic peptide can be performed using simple mixing under gentle conditions, such as physiological pH (e.g., pH 7.0 to 7.4) at room temperature (e.g., 25 ºC) or physiological temperature (e.g., 37 ºC). Optionally, the method can include combining the hydrogel components and therapeutic peptide with other components, such as a dispersing agent and / or an additional therapeutic agent (e.g., an antidiabetic agent or antiobesity agent). In some embodiments, the composition is prepared no more than 1 hour, 30 minutes, 15 minutes, 10 minutes, 5 minutes, 2 minutes, or 1 minute before administering the composition to the subject. Alternatively or in combination, the composition can be prepared at least 1 minute, 2 minutes, 5 minutes, 10 minutes, 15 minutes, 30 minutes, or 1 hour before administering the composition to the subject. The dynamic hydrogel can be mostly or fully formed before the composition is administered to the subject. For example, the dynamic hydrogel can be sufficiently crosslinked (e.g., non-covalently crosslinked) to exhibit the shear- thinning, self-healing, and / or viscoelastic properties described herein before the composition is administered to the subject. In some embodiments, the present technology provides kits for preparing a composition as described herein. The kit can include a solution containing the therapeutic peptide and one or more solutions containing the components of a dynamic hydrogel (e.g., a solution containing a polymer and a solution containing nanoparticles, or a single solution containing a polymer and nanoparticles). The therapeutic peptide solution can include a dispersing agent (e.g., a surfactant and / or a tonicity agent). Optionally, the kit can include a solution containing an additional therapeutic agent. The solutions can be provided in tubes, bottles, ampoules, syringes, or any other suitable storage container. In some embodiments, the solutions each independently include a suitable pharmaceutically acceptable diluent. The pharmaceutically acceptable diluent can be any diluent that does not substantially produce adverse reactions, e.g., toxic, allergic, or immunological reactions, when administered to a subject. Examples of pharmaceutically acceptable diluents include, but are not limited to, saline, Ringer’s solution, dextrose solution, phosphate buffered saline, water, or a combination thereof. The pharmaceutically acceptable diluent can include an isotonicity imparting agent, such as sodium chloride, potassium chloride, or monosodium phosphate. The pharmaceutically acceptable diluent can include a buffer, such as bicarbonate, TRIS, HEPES, MOPS, CHES, CHAPS, or phosphate buffered saline. The pharmaceutically acceptable diluent can include Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO stabilizers and / or preservatives, as appropriate. Additional examples and details of pharmaceutically acceptable diluents can be found in Martin, Remington’s Pharmaceutical Sciences, 21st Ed., Mack Publ. Co., Easton, Pa. (2005), which is incorporated herein by reference in its entirety. Examples The present technology is further illustrated by the following non-limiting examples. Example 1: Preparation of Incretin Mimetic Loaded PNP Hydrogels This example describes a process for preparing incretin mimetic loaded PNP hydrogels. Briefly, clinically used incretin mimics are dissolved in a buffer and mixed with polymeric nanoparticles, which are subsequently mixed with a hydrophobically modified cellulosic polymer to form a shear-thinning, self-healing hydrogel. Different incretin mimics can be used in the hydrogels, and additives can be included to stabilize the cargo and / or tune the release properties. Semaglutide, liraglutide, and tirzepatide are GLP-1 RAs carrying a single optimized fatty acid and linker modification enabling reversible binding to albumin to extend the circulating half-life while maintaining optimal potency. While reducing treatment frequency from daily to weekly is associated with improved patient adherence, there is still room for improvement to reduce treatment burden and improve patient compliance (FIG.2A). To address this challenge, long-acting formulations of semaglutide and tirzepatide were developed to provide continuous therapy for upwards of four months from a single administration to coincide with the typical cadence with which type 2 diabetes patients visit their endocrinologist or primary care provider (FIG.2B). HPMC (meets USP testing specifications), N,N-diisopropylethylamine (Hunig's base), hexanes, diethyl ether, N-methyl-2-pyrrolidone (NMP), dichloromethane (DCM), lactide (LA), 1-dodecylisocynate, and diazobicylcoundecene (DBU) were purchased from Sigma-Aldrich and used as received. Monomethoxy-PEG (5 kDa) was purchased from Sigma-Aldrich and was dried under vacuum prior to use. Glassware and stir bars were oven- dried at 180 °C. When specified, solvents were degassed by three cycles of freeze, pump, and thaw. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Dodecyl-modified (hydroxypropyl)methyl cellulose (HPMCíC12) was prepared as follows. HPMC (1.0 g) was dissolved in NMP (40 mL) by stirring at 80 °C for 1 h. Once the solution reached room temperature (RT), 1-dodecylisocynate (105 mg, 0.5 mmol) and N,N-diisopropylethylamine (catalyst, ~3 drops) were dissolved in NMP (5.0 mL). This solution was added dropwise to the reaction mixture, which was then stirred at RT for 16 h. This solution was then precipitated from acetone, decanted, redissolved in water (~2 wt%), and placed in a dialysis tube for dialysis for 3í4 days. The polymer was lyophilized and reconstituted to a 60-mg / mL solution with sterile PBS. PEG-PLA nanoparticles (PEG-PLA NPs) were prepared as follows. Monomethoxy-PEG (5 kDa; 0.25 g, 4.1 mmol) and DBU (15 μL, 0.1 mmol; 1.4 mol% relative to LA) were dissolved in anhydrous dichloromethane (1.0 mL). LA (1.0 g, 6.9 mmol) was dissolved in anhydrous DCM (3.0 mL) with mild heating. The LA solution was added rapidly to the PEG / DBU solution and was allowed to stir for 10 min. The reaction mixture was quenched and precipitated by a 1:1 hexane and ethyl ether solution. The synthesized PEGíPLA was collected and dried under vacuum. Hydrogel permeation chromatography (GPC) was used to verify that the molecular weight and dispersity of polymers met quality control (QC) parameters (FIG. 3A). A 1-mL solution of PEGíPLA in DMSO (50 mg / mL) was added dropwise to 10 mL of water at RT under a high stir rate (600 rpm). Nanoparticles were purified by centrifugation over a filter (molecular weight cutoff of 10 kDa; Millipore Amicon Ultra-15) followed by resuspension in PBS to a final concentration of 200 mg / mL. Nanoparticles were characterized by dynamic light scattering (DLS) to determine the nanoparticle diameter, 35 ± 4 nm (FIG.3B). Hydrogel formulations contained 1 wt% HPMCíC12 and 10 wt% PEGíPLA nanoparticles, and are denoted as PNP-1-10. These hydrogels were made by mixing a weighted ratio of 6 wt% HPMCíC12 polymer solution, 20 wt% nanoparticle solution, and PBS or water containing GLP-1 RAs (semaglutide, liraglutide, or tirzepatide). Semaglutide, liraglutide, and tirzepatide were obtained from the Stanford University Hospital Formulary as the drug products Ozempic® (Novo Nordisk), Victoza® (Eli Lilly), and Mounjaro® (Lilly), respectively. These drug products were provided as aqueous formulations including phosphate buffer, tonicity agents such as propylene glycol (Ozempic® and Victoza®) or saline (Mounjaro®), and preservatives such as phenol. These formulations were lyophilized and then Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO resuspended in water to formulate the hydrogels. For formulations including Tween-20 and / or Į-cyclodextrin (aCD), these additives were mixed with the GLP-1 RAs, and the resulting solution was mixed with the nanoparticles. The nanoparticles and aqueous components were loaded into one syringe, the HPMC-C12 was loaded into a second syringe and components were mixed using an elbow connector (FIG. 4). After mixing, the elbow was replaced with a 21-gauge needle for injection. The semaglutide, liraglutide, and tirzepatide hydrogel formulations and their corresponding components are listed in Tables 2A and 2B, 3A and 3B, and 4A and 4B below, respectively. Table 2A: Semaglutide PNP hydrogel formulations SemaglutideHPMC-C12 Tween-20 PEG-PLA Propylene NPs Glyc Phenol (^g / mL) (mg / mL) (mg / mL) ol (^g / mL) (mg / mL)(mg / mL)PNP-S-1.2 mg 2-10 1200 20 0 100 0 0 PNP-S-1.8 mg 2-10 1800 20 0 100 0 0 PNP-S-2.4 mg 2-10 2400 20 0 100 0 0 PNP-S-1.2 mg 1-10 1200 10 0 100 0 0 PNP-S-1.8 mg 1-10 1800 10 0 100 0 0 PNP-S-2.4 mg 1-10 2400 10 0 100 0 0 PNP-1-10-S1 1800 10 0 100 18.9 7.425 PNP-1-10-S2 1800 10 0.55 100 18.9 7.425 PNP-1-10-S3 1800 10 1.1 100 18.9 7.425 PNP-1-10-S4 1800 10 0 100 18.9 7.425 PNP-1-10-S5 1800 10 0 100 18.9 7.425 PNP-1-10-S6 1800 10 0 100 18.9 7.425 PNP-1-10-S7 1800 10 0.55 100 18.9 7.425 PNP-1-10-S8 1800 10 0.825 100 18.9 7.425 PNP-1-10-S9 1800 10 1.1 100 18.9 7.425 PNP-1-10-S10 1800 10 0.55 100 18.9 7.425 Table 2B: Semaglutide PNP hydrogel formulations SodiumSodium Potassium Chloride Phosphate Phosphate (mg / mL) (mg / mL) (mg / mL) PNP-S-1.2 mg 2-10 9.72 0.859 0.156 PNP-S-1.8 mg 2-10 9.27 0.819 0.148 PNP-S-2.4 mg 2-10 9.18 0.811 0.147 PNP-S-1.2 mg 1-10 9.81 0.867 0.157 0 0 PNP-S-1.8 mg 1-10 9.36 0.827 0.150 0 0 PNP-S-2.4 mg 1-10 9.27 0.819 0.148 0 0 PNP-1-10-S1 8.01 2.625 0.128 0 0 PNP-1-10-S2 8.006 2.624 0.128 0 0 PNP-1-10-S3 8.001 2.624 0.128 0 0 Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO PNP-1-10-S4 8.006 2.624 0.128 0.521 0 PNP-1-10-S5 8.001 2.624 0.128 1.042 0 PNP-1-10-S6 0 1.917 0 0 0 PNP-1-10-S7 0 1.917 0 0 0 PNP-1-10-S8 0 1.917 0 0 0 PNP-1-10-S9 0 1.917 0 0 0 PNP-1-10-S10 0 1.917 0 0 3.59 Table 3A: Liraglutide PNP hydrogel formulations LiraglutideHPMC-C12 Tween-20 PEG-PLA NPs (^g / mL) (mg / mL) (mg / mL) (^g / mL) PNP-1-10-L1 1800 10 0 100 PNP-2-10-L1 1800 20 0 100 Table 3B: Liraglutide PNP hydrogel formulations Propylenecol Phen Sodium Potassium Gly ol Sodium Chloride / mL) (mg / mL) Phosphate Phosphate (mg (mg / mL) (mg / mL) (mg / mL) PNP-1-10-L1 0 0 9.36 0.827 0.150 PNP-2-10-L1 0 0 9.27 0.819 0.148 Table 4A: Tirzepatide PNP hydrogel formulations TirzepatideHPMC-C12 Tween-20 PEG-PLA NPs (^g / mL) (mg / mL) (mg / mL) (^g / mL) PNP-1-10-T1 280 10 0 100 PNP-1-10-T2 1800 10 0 100 PNP-1-10-T3 1800 10 0.55 100 PNP-1-10-T4 1800 10 1.1 100 PNP-1-10-T5 280 10 0 100 PNP-1-10-T7 1800 10 0.55 100 PNP-1-10-T8 1800 10 1.1 100 PNP-1-10-T9 4500 10 0 100 PNP-1-10-T10 4500 10 0 100 PNP-1-10-T11 4500 10 0.55 100 PNP-1-10-T12 4500 10 1.1 100 Table 4B: Tirzepatide PNP hydrogel formulations PropyleneSodium Sodium Potassium Glycol Chloride Phosphate Phosphate PNP-1-10-T2 0 9.240 0.918 0.128 PNP-1-10-T3 0 9.236 0.917 0.128 PNP-1-10-T4 0 9.231 0.917 0.128 PNP-1-10-T5 0 0.191 0.033 0 PNP-1-10-T7 0 1.230 0.210 0 PNP-1-10-T8 0 1.230 0.210 0 Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO PNP-1-10-T9 21.9 1.230 0.210 0 PNP-1-10-T10 39.2 1.230 0.210 0 PNP-1-10-T11 0 1.230 0.210 0 PNP-1-10-T12 0 1.230 0.210 0 Example 2: Rheological Characterization of Incretin Mimetic Loaded PNP Hydrogels This example describes rheological characterization of PNP hydrogels loaded with incretin mimetics. Rheological testing was performed using a 20-mm-diameter serrated parallel plate at a 600-^m gap on a stress-controlled TA Instruments DHR-2 rheometer. All experiments were performed at 25 °C. Frequency sweeps were performed from 0.1 to 100 rad / s with a constant oscillation strain within the linear viscoelastic regime (1%). Amplitude sweeps were performed at a constant angular frequency of 10 rad / s from 0.01% to 10000% strain with a gap height of 500 μm. Flow sweeps were performed from low to high stress with steady-state sensing. Steady shear experiments were performed by alternating between a low shear rate (0.1 sí1) and high shear rate (10 sí1) for 60 s each for three full cycles. Shear rate sweep experiments were performed from 10 to 0.001 sí1. Stress controlled yield stress measurements (stress sweeps) were performed from low to high stress with steady-state sensing and 10 points per decade. FIGS.5A and 5B are graphs showing rheological characterization of PNP-1-10 hydrogel formulations with varying concentrations of semaglutide: frequency-dependent oscillatory shear sweep (FIG.5A) and stress-dependent oscillatory shear sweep (FIG.5B). FIGS.6A and 6B are graphs showing rheological characterization of PNP-2-10 hydrogel formulations with varying concentrations of semaglutide: frequency-dependent oscillatory shear sweep (FIG.6A) and stress-dependent oscillatory shear sweep (FIG.6B). FIGS. 7A–7C are graphs showing rheological characterization of PNP-1-10 hydrogel formulations with varying concentrations of tirzepatide: frequency-dependent oscillatory shear sweep (FIG. 7A and 7C) and stress-dependent oscillatory shear sweep (FIG. 7B). In FIG.7C, PNP-TZP-4.5 mg 1-10 corresponds to PNP-1-10-T9, PNP-TZP-0.28 mg 1-10 corresponds to PNP-1-10-T5, PNP-TZP-4.5 mg 0.1 wt% tween 1-10 corresponds to PNP-1- 10-T11, and PNP-TZP-4.5 mg 0.1 wt% tween 1-10 corresponds to PNP-1-10-T12. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO These results demonstrate that addition of the GLP-1 RAs and other formulation excipients did not affect the mechanical behaviors of the hydrogels. Example 3: In Vitro Release Kinetics of Semaglutide from PNP Hydrogel Formulations This example describes in vitro characterization of release of semaglutide from PNP hydrogel formulations. An in vitro release assay was used to study release behaviors of semaglutide from PNP hydrogels (FIG.8A).100 μL of each hydrogel formulation was loaded into four-inch capillaries and 400 μL of PBS medium was added slowly on top. The surrounding PBS was removed for analysis after 1, 3, 6, 12, 24, and 48 hours and at one week and two weeks after injection into the capillary, and fresh PBS was replaced after each aliquot removal. Semaglutide was quantified by ELISA to determine release kinetics over time. FIGS. 8B and 8C are graphs of in vitro release profiles showing the % cumulative release of semaglutide from PNP-2-10 (FIG.8B) and PNP-1-10 (FIG.8C) hydrogel formulations at low, medium, and high semaglutide loadings, over the course of two weeks. For all formulations, a significant proportion of the semaglutide cargo was released over the two-week period. These results suggest that the semaglutide-loaded hydrogels may contain a significant fraction of “free” cargo (not adhered to the PNP hydrogel matrix) that undergoes fast, diffusion-based release. Semaglutide may form robust dimeric species at formulation- relevant concentrations, and these dimers were hypothesized to constitute the “free” fraction of the drug cargo. Semaglutide dimers are sufficiently small (RH < 2 nm) to be released over relatively short timeframes from the PNP hydrogels on account of its comparatively large mesh size (^~3.5 nm). FIG.8D is a graph of in vitro release profiles showing the % cumulative release of semaglutide from various PNP-1-10 hydrogel formulations over the course of two weeks, showing the effect of Tween-20 addition on semaglutide release in the presence of propylene glycol and saline. All formulations exhibited low levels of burst release and high cargo retention over the two-week period attributable primarily to the presence of propylene glycol. The release rate was further reduced with increasing amounts of Tween-20. It is hypothesized that propylene glycol and Tween-20 act as dispersing agents to inhibit the formation of semaglutide dimers, thus promoting stronger binding of the fatty acid side chain of semaglutide to the PNP hydrogel matrix. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO FIG.8E is a graph of in vitro release profiles showing the % cumulative release of semaglutide from various PNP-1-10 hydrogel formulations over the course of two weeks, showing that there is negligible effect of Į-cyclodextrin (aCD) addition on semaglutide release in the presence of propylene glycol and saline. All formulations exhibited low levels of burst release and high cargo retention over the two-week period. FIG.8F is a graph of in vitro release profiles showing the % cumulative release of semaglutide from various PNP-1-10 hydrogel formulations over the course of two weeks, showing the effect of Tween-20 addition on semaglutide release in the presence of propylene glycol and absence of saline. All formulations exhibited low levels of burst release and high cargo retention over the two-week period attributable primarily to the presence of propylene glycol. The release rate was further reduced with increasing amounts of Tween-20. Formulations including Tween-20 in the absence of saline exhibited modest improvements in cargo retention, compared to formulations including Tween-20 in the presence of saline (FIG. 8D). The presence of saline may increase hydrophobic effects that promote dimerization of semaglutide. Thus, removal of saline prior to formulation into to the hydrogel may facilitate breaking up of semaglutide dimers and improve binding of semaglutide to the hydrogel. FIG.8G is a graph of in vitro release profiles showing the % cumulative release of semaglutide from various PNP-1-10 hydrogel formulations, showing the effect of bovine serum albumin (BSA) in the release buffer and in the hydrogel. The PNP-1-10-S7 hydrogel formulation was prepared without BSA in the hydrogel, and with or without 1% BSA in the PBS release buffer. The PNP-1-10-S10 hydrogel formulation was prepared with 3.59 mg / mL BSA in the hydrogel and without BSA in the release buffer. The PNP-1-10-S16 formulation was prepared without BSA in the release buffer or in the hydrogel. No significant differences in release rate were observed between the various groups, thus indicating that the presence of BSA around the hydrogels does not affect semaglutide release. Example 4: In Vitro Release Kinetics of Liraglutide from PNP Hydrogel Formulations This example describes in vitro characterization of release of liraglutide from PNP hydrogel formulations. The in vitro release assay of Example 3 was used to study release behaviors of liraglutide from PNP hydrogels. FIG.9 is a graph illustrating in vitro release profiles showing the % cumulative release of liraglutide from 1.8 mg / mL PNP-1-10 and PNP-2-10 hydrogel formulations, over Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO the course of two weeks. The formulations exhibited negligible and high cargo retention over the two-week period, even in the absence of propylene glycol and Tween-20. It was hypothesized that essentially all of the liraglutide was “bound” cargo that was adhered to the PNP hydrogel structure and would be primarily released by hydrogel erosion, which is severely limited in this capillary release model. The fatty acid side chain of liraglutide may drive the formation of more disorganized heptameric structures at micromolar concentrations, thus allowing the liraglutide to associate more strongly with the structural motifs within the PNP hydrogels even in the absence of a dispersing agent. Example 5: In Vitro Release Kinetics of Tirzepatide from PNP Hydrogel Formulations This example describes in vitro characterization of release of tirzepatide from PNP hydrogel formulations. The in vitro release assay of Example 3 is used to study release behaviors of tirzepatide from PNP hydrogels. The formulations exhibit low levels of burst release and high cargo retention over the two-week period. Example 6: In Vitro Release Kinetics of PNP Hydrogels Formulated with Liraglutide and Insulin Glargine This example describes in vitro characterization of release of liraglutide and insulin glargine from PNP hydrogel formulations. Insulin glargine was obtained from the Stanford University Hospital Formulary as the drug product Lantus® (Sanofi). PNP-1-10 hydrogels with and without liraglutide and / or insulin glargine were prepared according to the protocol of Example 1. The in vitro release assay of Example 3 was used to study release behaviors of liraglutide and insulin glargine from PNP hydrogels. The hydrogel formulations and their corresponding components are listed in Tables 5A and 5B below. Table 5A: Liraglutide and Lantus PNP hydrogel formulations LiraglutideLantus HPMC- PEG- Propylene C12 PLA NPs G Phenol Zinc (^g / mL)(^g / mL) lycol (mg / mL) (^g / mL) (mg / mL) (mg / mL) (mg / mL) PNP-1-10-LIRA 1800 0 10 100 4.32 1.697 0. PNP-1-10-LIRA-LAN 1800 1004 10 100 4.32 1.697 0.828 PNP-1-10-LAN 0 1004 10 100 0 0 0.828 Table 5B: Liraglutide and Lantus PNP hydrogel formulations Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO MetacresolGlycerol Sodium Sodium (mg / mL)(85%, Tween-20 Potassium (mg / m Chloride Phosphate Phosphate mg / mL) L) (mg / mL) (mg / mL) (mg / mL) PNP-1-10-LIRA 0 0 0 8.010 1.146 0.128 PNP-1-10-LIRA-LAN 0.075 0.552 0.552 5.526 0.926 0.088 PNP-1-10-LAN 0.075 0.552 0.552 5.526 0.488 0.088 FIG.10 is a graph illustrating in vitro release profiles showing the % cumulative release of liraglutide and Lantus from PNP-1-10 hydrogel formulations measured via ELISA, over the course of two weeks. All formulations exhibited low levels of burst release and high cargo retention over the two-week period, indicating that both liraglutide and insulin glargine could be successfully encapsulated in PNP hydrogels. Example 7: In Vivo Characterization of Incretin Mimetic Loaded PNP Hydrogel Formulations This example describes characterization of the in vivo pharmacokinetics, pharmacodynamics, and biocompatibility of incretin mimetic loaded PNP hydrogel formulations in diabetic rats. Male Sprague Dawley rats 160–230 g (8–10 weeks, Charles River) were weighed and fasted in the morning 6–8 h prior to treatment with nicotinamide (NA) and streptozotocin (STZ). NA was dissolved in 1X PBS and administered intraperitoneally at 110 mg / kg. STZ is diluted to 10 mg / mL in sodium citrate buffer immediately before injection. STZ solution was injected intraperitoneally at 65 mg / kg into each rat. Rats were provided with water containing 10% sucrose for 24 h after injection with STZ. Rat blood glucose (BG) levels were tested for hyperglycemia daily after the STZ treatment via tail vein blood collection using a handheld blood glucose monitor (Bayer Contour Next). Type 2 diabetes (T2D) is defined as having three consecutive BG measurements in the range of 130–200 mg / dL in non-fasted rats. Diabetic rats received either a) a single subcutaneous injection of a PNP hydrogel loaded with semaglutide (1.85 mg / mL) (PNP-1-10-S7 in Tables 2A and 2B) or tirzepatide (4.5 mg / mL) (PNP-1-10-T11 in Tables 4A and 4B); or b) daily subcutaneous bolus injections of either PBS, 20 μg semaglutide, or 50 μg tirzepatide. For each of the treatment groups, baseline blood was collected from the tail vein at day zero and daily blood glucose measurements are taken from the tail vein using a handheld blood glucose monitor (Bayer Contour Next) for 42 days following treatment. Blood glucose was measured, immediately followed by blood samples collected from the tail vein, every day for the first seven days of the study to measure serum semaglutide or tirzepatide concentrations using ELISA, and two Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO times a week, thereafter. Plasma GLP-1 RA concentrations were measured by ELISA at each time-point and total bioavailability of semaglutide or tirzepatide were determined at the end- point of the study. An oral glucose tolerance test was used to group rats according to the glucose tolerance before treatment (at day -1). FIG.11 is a schematic illustration of the treatment schedule and timing of blood glucose measurements and serum collection for analysis. Diabetic rats received either a single subcutaneous injection of a semaglutide- or tirzepatide-loaded PNP hydrogel, or daily subcutaneous bolus injections of PBS, 20 μg daily semaglutide, or 50 μg tirzepatide. FIGS. 12A and 12B are graphs illustrating the results of oral glucose tolerance testing before treatment (FIG.12A) and after 6 weeks of treatment (FIG.12B). An oral glucose tolerance test (OGTT) was conducted to group diabetic rats into treatment groups. Rats were fasted before administration of a glucose load by oral gavage. Baseline (fasting) blood glucose measurements were taken before glucose administration and measurements were made at regular intervals thereafter. Blood glucose was measured at –5, 0, 5, 15, 30, 45, 60, and 120 min. Using the area under the curve (AUC), rats with similar glucose tolerance were paired and then randomized into treatment groups. FIG.13 is a graph illustrating the percent change in blood glucose (BG) levels for rats treated with PNP hydrogels versus bolus injections. A single administration of semaglutide PNP or tirzepatide PNP hydrogel reduced the BG of type 2-like diabetic male rats over the course of 6 weeks, compared to daily PBS bolus injections. The plot shows change in BG over 6 weeks following each treatment group regimen (n = 6). FIG.14 is a graph illustrating the percent change in weight for rats treated with PNP hydrogels versus bolus injections. A single administration of semaglutide PNP or tirzepatide PNP hydrogel reduced the overall weight gain in type 2-like diabetic male rats over the course of 6 weeks post treatment, compared to daily PBS bolus injections. The plot shows change in weight over 6 weeks of each treatment group (n = 6). FIG.15 is a graph illustrating pharmacokinetics of a 20 μg daily bolus injection of semaglutide versus a PNP hydrogel (PNP-1-10 with a 1.8 mg / mL semaglutide loading and 0.05 wt% Tween-20) in male diabetic rats (n = 6) over the course of 6 weeks post treatment. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO FIG.16 is a graph illustrating pharmacokinetics of a 20 μg daily bolus injection of semaglutide versus a PNP hydrogel (PNP-1-10 with a 1.8 mg / mL semaglutide loading and 0.05 wt% Tween-20) over the first 48 hours, overlaid with the 24 hour pharmacokinetics of a 20 μg intravenous (I.V.) and subcutaneous (S.C.) bolus injection in male diabetic rats (n = 6). FIG. 17 shows graphs illustrating an assessment of treatment biocompatibility using blood chemistry to look for negative effects on the liver or kidney and evaluating the effect of treatment on hemoglobin A1C (HbA1c). Blood was collected pre- and post-treatment (after 6 weeks). Liver toxicity was assessed through measurement of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin. Kidney toxicity was evaluated by examining creatinine and blood urea nitrogen (BUN) levels. Values for ALT, AST, creatine, and BUN were within the range of healthy rats (defined as the mean ± 2 standard deviations) for both the treatment and control groups. These results indicate that the hydrogel formulations effectively maintained therapeutically relevant concentrations of semaglutide and tirzepatide throughout the duration of the six-week-long study. Hydrogel-based treatments resulted in a significant reduction in average BG and body weight over the course of the study relative to PBS bolus injection controls. The reduction in average BG and body weight was comparable to the reduction achieved by treatments with daily semaglutide and tirzepatide bolus injections. Hydrogel-based treatments were shown to be well tolerated, exhibiting no observable differences in liver and kidney compared to untreated animals. Additional Examples Additional examples of aspects of the present technology are described below as numbered clauses (1, 2, 3, etc.) for convenience. These are provided as examples and do not limit the subject technology. Clause 1. A composition for treating a disease or condition, the composition comprising: a dynamic hydrogel comprising a polymer and a plurality of nanoparticles, wherein the polymer is non-covalently crosslinked with the plurality of nanoparticles; and an acylated peptide encapsulated by the dynamic hydrogel. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 2. The composition of Clause 1, wherein the acylated peptide includes a lipophilic substituent. Clause 3. The composition of Clause 2, wherein the acylated peptide is encapsulated in the dynamic hydrogel via interactions between the lipophilic substituent and the dynamic hydrogel. Clause 4. The composition of Clause 3, wherein the plurality of nanoparticles have hydrophobic surfaces that interact with the lipophilic substituent of the dynamic hydrogel. Clause 5. The composition of any one of Clauses 2 to 4, wherein the lipophilic substituent comprises an acyl group of a fatty acid. Clause 6. The composition of Clause 5, wherein the fatty acid is a C4 fatty acid, a C6 fatty acid, a C8 fatty acid, a C10 fatty acid, a C12 fatty acid, a C14 fatty acid, a C15 fatty acid, a C16 fatty acid, a C17 fatty acid, a C18 fatty acid, a C20 fatty acid, a C22 fatty acid, a C24 fatty acid, a C26 fatty acid, a C28 fatty acid, a C30 fatty acid, a C32 fatty acid, a C34 fatty acid, a C36 fatty acid, or a C38 fatty acid. Clause 7. The composition of any one of Clauses 2 to 6, further comprising a binding agent that interacts with the lipophilic substituent to physically entrap the acylated peptide in the dynamic hydrogel. Clause 8. The composition of Clause 7, wherein the binding agent comprises albumin. Clause 9. The composition of Clause 7 or 8, wherein the binding agent is larger than a mesh size of the dynamic hydrogel. Clause 10. The composition of any one of Clauses 1 to 9, wherein the acylated peptide is smaller than a mesh size of the dynamic hydrogel. Clause 11. The composition of any one of Clauses 1 to 10, further comprising a dispersing agent that inhibits aggregation of the acylated peptide. Clause 12. The composition of Clause 11, wherein the dispersing agent comprises one or more of a surfactant or a tonicity agent. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 13. The composition of Clause 12, wherein the dispersing agent comprises the surfactant, and the surfactant comprises one or more of a polysorbate, a sorbitan fatty acid ester, a poloxamer, a polyoxyethylene alkyl ether, an alkyl sulfate, a fatty acid, a fatty acid alcohol, or a phospholipid. Clause 14. The composition of Clause 12 or 13, wherein the dispersing agent comprises the tonicity agent, and the tonicity agent comprises one or more of propylene glycol, glycerol, or mannitol. Clause 15. The composition of any one of Clauses 12 to 14, wherein a concentration of the dispersing agent in the composition is within a range from 0.1 mg / mL to 5 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, or 16 mg / mL to 26 mg / mL. Clause 16. The composition of any one of Clauses 1 to 15, wherein the acylated peptide comprises an incretin mimetic. Clause 17. The composition of Clause 16, wherein the incretin mimetic comprises a glucagon-like peptide-1 receptor agonist (GLP-1 RA). Clause 18. The composition of Clause 17, wherein the GLP-1 RA comprises one or more of liraglutide, semaglutide, ecnoglutide, cotadutide, mazdutide, tirzepatide, or retatrutide. Clause 19. The composition of any one of Clauses 16 to 18, wherein the incretin mimetic binds exclusively to a GLP-1 receptor. Clause 20. The composition of any one of Clauses 16 to 18, wherein the incretin mimetic binds to a GLP-1 receptor and at least one additional receptor. Clause 21. The composition of Clause 20, wherein the at least one additional receptor comprises one or more of a glucagon receptor or a gastric inhibitory peptide (GIP) receptor. Clause 22. The composition of any one of Clauses 1 to 15, wherein the acylated peptide comprises an analogue of a proglucagon-derived peptide. Clause 23. The composition of any one of Clauses 1 to 15, wherein the acylated peptide comprises an amylin analogue. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 24. The composition of any one of Clauses 1 to 15, wherein the acylated peptide comprises an insulin analogue. Clause 25. The composition of any one of Clauses 1 to 24, wherein the composition comprises from 1 mg to 250 mg of the acylated peptide. Clause 26. The composition of any one of Clauses 1 to 25, wherein a concentration of the acylated peptide in the composition is within a range from 1 mg / mL to 200 mg / mL. Clause 27. The composition of any one of Clauses 1 to 26, wherein the polymer comprises a hydrophobically-modified polysaccharide. Clause 28. The composition of Clause 27, wherein the hydrophobically- modified polysaccharide comprises a hydrophobically-modified cellulose derivative. Clause 29. The composition of Clause 28, wherein the hydrophobically- modified cellulose derivative is dodecyl-modified hydroxypropylmethylcellulose (HPMC- C12). Clause 30. The composition of any one of Clauses 1 to 29, wherein the plurality of nanoparticles comprise a plurality of polymeric nanoparticles. Clause 31. The composition of Clause 30, wherein the plurality of polymeric nanoparticles are amphiphilic. Clause 32. The composition of Clause 30 or 31, wherein the plurality of polymeric nanoparticles are poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) nanoparticles. Clause 33. The composition of any one of Clauses 1 to 32, wherein a concentration of the polymer in the dynamic hydrogel is within a range from 0.5 wt% to 5 wt%, 0.5 wt% to 4 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1 wt%, 1 wt% to 5 wt%, 1 wt% to 4 wt%, 1 wt% to 3 wt%, 1 wt% to 2 wt%, 2 wt% to 5 wt%, 2 wt% to 4 wt%, 2 wt% to 3 wt%, 3 wt% to 5 wt%, 3 wt% to 4 wt%, or 4 wt% to 5 wt%. Clause 34. The composition of any one of Clauses 1 to 33, wherein a concentration of the nanoparticles in the dynamic hydrogel is within a range from 1 wt% to 12 wt%, 1 wt% to 10 wt%, 1 wt% to 8 wt%, 1 wt% to 5 wt%, 1 wt% to 3 wt%, 3 wt% to 12 wt%, Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 3 wt% to 10 wt%, 3 wt% to 8 wt%, 3 wt% to 5 wt%, 5 wt % to 12 wt%, 5 wt% to 10 wt%, 5 wt% to 8 wt%, 8 wt% to 12 wt%, 8 wt% to 10 wt%, or 10 wt% to 12 wt%. Clause 35. The composition of any one of Clauses 1 to 34, wherein the dynamic hydrogel encapsulating the acylated peptide has a storage modulus within a range from 10 Pa to 1000 Pa, or 50 Pa to 500 Pa when measured at 25 °C over an angular frequency of 0.1 rad / s to 100 rad / s within a linear viscoelastic region of the dynamic hydrogel. Clause 36. The composition of any one of Clauses 1 to 35, wherein the dynamic hydrogel encapsulating the acylated peptide has a yield stress within a range from 1 Pa to 500 Pa, or 20 Pa to 200 Pa when measured at 25 °C. Clause 37. The composition of any one of Clauses 1 to 36, wherein the dynamic hydrogel encapsulating the acylated peptide has a viscosity within a range from 100 mPa-s to 1000 mPa-s when measured at 25 °C at a shear rate of 1000 s-1. Clause 38. The composition of any one of Clauses 1 to 37, wherein, upon administration to a subject, the composition delivers the acylated peptide to the subject over a treatment period of at least 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 28 days, 35 days, 40 days, 50 days, 60 days, 70 days, 80 days, 90 days, 100 days, 110 days, 120 days, 150 days, 180 days, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or 1 year. Clause 39. The composition of any one of Clauses 1 to 38, wherein, upon administration to a subject, the composition delivers the acylated peptide at a rate to the subject within a range from 0.25 mg / week to 25 mg / week, 0.5 mg / week to 20 mg / week, 0.5 mg / week to 2 mg / week, 0.5 mg / week to 1.5 mg / week, 1 mg / week to 2 mg / week, 2 mg / week to 5 mg / week, 5 mg / week to 15 mg / week, 5 mg / week to 10 mg / week, 10 mg / week to 20 mg / week, 10 mg / week to 15 mg / week, 12 mg / week to 25 mg / week, 12 mg / week to 15 mg / week, 15 mg / week to 25 mg / week, 15 mg / week to 20 mg / week, or 20 mg / week to 25 mg / week. Clause 40. The composition of any one of Clauses 1 to 39, wherein, upon administration to a subject, the composition produces an average concentration of the acylated peptide in serum of the subject within a range from 50 ng / mL to 500 ng / mL, 100 ng / mL to 300 ng / mL, or 150 ng / mL to 250 ng / mL. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 41. The composition of any one of Clauses 1 to 40, wherein, upon administration to a subject, the composition produces a Cmax of the acylated peptide in serum of the subject less than or equal to 2000 ng / mL. Clause 42. The composition of any one of Clauses 1 to 41, wherein the composition is configured for administration via subcutaneous injection. Clause 43. The composition of any one of Clauses 1 to 42, wherein the disease or condition comprises diabetes or a diabetes-related condition. Clause 44. The composition of Clause 43, wherein the diabetes or diabetes- related condition comprises prediabetes, type I diabetes, type II diabetes, hyperglycemia, or impaired glucose tolerance. Clause 45. The composition of any one of Clauses 1 to 44, wherein the disease or condition comprises one or more of obesity, excessive body weight, an eating disorder, or obstructive sleep apnea. Clause 46. The composition of any one of Clauses 1 to 45, wherein the disease or condition comprises one or more of the following: a cardiovascular disease, a liver disease, a neurological or neurodegenerative disease, an inflammatory disease, a renal disease, a bone disease, a hormonal disease, or a gastrointestinal disease. Clause 47. A method of treating a disease or condition, the method comprising: administering a composition to a subject, wherein the composition comprises: a dynamic hydrogel comprising a polymer and a plurality of nanoparticles, wherein the polymer is non-covalently crosslinked with the plurality of nanoparticles, and an acylated peptide encapsulated by the dynamic hydrogel. Clause 48. The method of Clause 47, wherein the acylated peptide includes a lipophilic substituent. Clause 49. The method of Clause 48, wherein the acylated peptide is encapsulated in the dynamic hydrogel via interactions between the lipophilic substituent and the dynamic hydrogel. Clause 50. The method of Clause 49, wherein the plurality of nanoparticles have hydrophobic surfaces that interact with the lipophilic substituent of the dynamic hydrogel. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 51. The method of any one of Clauses 48 to 50, wherein the lipophilic substituent comprises an acyl group of a fatty acid. Clause 52. The method of Clause 51, wherein the fatty acid is a C4 fatty acid, a C6 fatty acid, a C8 fatty acid, a C10 fatty acid, a C12 fatty acid, a C14 fatty acid, a C15 fatty acid, a C16 fatty acid, a C17 fatty acid, a C18 fatty acid, a C20 fatty acid, a C22 fatty acid, a C24 fatty acid, a C26 fatty acid, a C28 fatty acid, a C30 fatty acid, a C32 fatty acid, a C34 fatty acid, a C36 fatty acid, or a C38 fatty acid. Clause 53. The method of any one of Clauses 48 to 52, further comprising a binding agent that interacts with the lipophilic substituent to physically entrap the acylated peptide in the dynamic hydrogel. Clause 54. The method of Clause 53, wherein the binding agent comprises albumin. Clause 55. The composition of Clause 53 or 54, wherein the binding agent is larger than a mesh size of the dynamic hydrogel. Clause 56. The method of any one of Clauses 47 to 55, wherein the acylated peptide is smaller than a mesh size of the dynamic hydrogel. Clause 57. The method of any one of Clauses 47 to 56, further comprising a dispersing agent that inhibits aggregation of the acylated peptide. Clause 58. The method of Clause 57, wherein the dispersing agent comprises one or more of a surfactant or a tonicity agent. Clause 59. The method of Clause 58, wherein the dispersing agent comprises the surfactant, and the surfactant comprises one or more of a polysorbate, a sorbitan fatty acid ester, a poloxamer, a polyoxyethylene alkyl ether, an alkyl sulfate or a salt thereof, a fatty acid, a fatty acid alcohol. Clause 60. The method of Clause 58 or 59, wherein the dispersing agent comprises the tonicity agent, and the tonicity agent comprises one or more of propylene glycol, glycerol, or mannitol. Clause 61. The method of any one of Clauses 58 to 60, wherein a concentration of the dispersing agent in the composition is within a range from 0.1 mg / mL to Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 5 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, or 16 mg / mL to 26 mg / mL. Clause 62. The method of any one of Clauses 47 to 61, wherein the acylated peptide comprises an incretin mimetic. Clause 63. The method of Clause 62, wherein the incretin mimetic comprises a glucagon-like peptide-1 receptor agonist (GLP-1 RA). Clause 64. The method of Clause 63, wherein the GLP-1 RA comprises one or more of liraglutide, semaglutide, ecnoglutide, cotadutide, mazdutide, tirzepatide, or retatrutide. Clause 65. The method of any one of Clauses 62 to 64, wherein the incretin mimetic binds exclusively to a GLP-1 receptor. Clause 66. The method of any one of Clauses 62 to 64, wherein the incretin mimetic binds to a GLP-1 receptor and at least one additional receptor. Clause 67. The method of Clause 66, wherein the at least one additional receptor comprises one or more of a glucagon receptor or a gastric inhibitory peptide (GIP) receptor. Clause 68. The method of any one of Clauses 47 to 67, wherein the acylated peptide comprises an analogue of a proglucagon-derived peptide. Clause 69. The method of any one of Clauses 47 to 67, wherein the acylated peptide comprises an amylin analogue. Clause 70. The method of any one of Clauses 47-67 or 69, wherein the acylated peptide comprises an insulin analogue. Clause 71. The method of any one of Clauses 47 to 70, wherein the composition comprises from 1 mg to 250 mg of the acylated peptide. Clause 72. The method of any one of Clauses 47 to 71, wherein a concentration of the acylated peptide in the composition is within a range from 1 mg / mL to 200 mg / mL. Clause 73. The method of any one of Clauses 47 to 72, wherein the polymer comprises a hydrophobically-modified polysaccharide. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 74. The method of Clause 73, wherein the hydrophobically-modified polysaccharide comprises a hydrophobically-modified cellulose derivative. Clause 75. The method of Clause 74, wherein the hydrophobically-modified cellulose derivative is dodecyl-modified hydroxypropylmethylcellulose (HPMC-C12). Clause 76. The method of any one of Clauses 47 to 75, wherein the plurality of nanoparticles comprise a plurality of polymeric nanoparticles. Clause 77. The method of Clause 76, wherein the plurality of polymeric nanoparticles are amphiphilic. Clause 78. The method of Clause 76 or 77, wherein the plurality of polymeric nanoparticles are poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) nanoparticles. Clause 79. The method of any one of Clauses 47 to 78, wherein a concentration of the polymer in the dynamic hydrogel is within a range from 0.5 wt% to 5 wt%, 0.5 wt% to 4 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1 wt%, 1 wt% to 5 wt%, 1 wt% to 4 wt%, 1 wt% to 3 wt%, 1 wt% to 2 wt%, 2 wt% to 5 wt%, 2 wt% to 4 wt%, 2 wt% to 3 wt%, 3 wt% to 5 wt%, 3 wt% to 4 wt%, or 4 wt% to 5 wt%. Clause 80. The method of any one of Clauses 47 to 79, wherein a concentration of the nanoparticles in the dynamic hydrogel is within a range from 1 wt% to 12 wt%, 1 wt% to 10 wt%, 1 wt% to 8 wt%, 1 wt% to 5 wt%, 1 wt% to 3 wt%, 3 wt% to 12 wt%, 3 wt% to 10 wt%, 3 wt% to 8 wt%, 3 wt% to 5 wt%, 5 wt % to 12 wt%, 5 wt% to 10 wt%, 5 wt% to 8 wt%, 8 wt% to 12 wt%, 8 wt% to 10 wt%, or 10 wt% to 12 wt%. Clause 81. The method of any one of Clauses 47 to 80, wherein the dynamic hydrogel encapsulating the acylated peptide has a storage modulus within a range from 10 Pa to 1000 Pa, or 50 Pa to 500 Pa when measured at 25 °C over an angular frequency of 0.1 rad / s to 100 rad / s within a linear viscoelastic region of the dynamic hydrogel. Clause 82. The method of any one of Clauses 47 to 81, wherein the dynamic hydrogel encapsulating the acylated peptide has a yield stress within a range from 1 Pa to 500 Pa, or 20 Pa to 200 Pa when measured at 25 °C. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 83. The method of any one of Clauses 47 to 82, wherein the dynamic hydrogel encapsulating the acylated peptide has a viscosity within a range from 100 mPa-s to 1000 mPa-s when measured at 25 °C at a shear rate of 1000 s-1. Clause 84. The method of any one of Clauses 47 to 83, wherein, upon administration to the subject, the composition delivers the acylated peptide to the subject over a treatment period of at least 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 28 days, 35 days, 40 days, 50 days, 60 days, 70 days, 80 days, 90 days, 100 days, 110 days, 120 days, 150 days, 180 days, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or 1 year. Clause 85. The method of any one of Clauses 47 to 84, wherein, upon administration to the subject, the composition delivers the acylated peptide at a rate to the subject within a range from 0.25 mg / week to 25 mg / week, 0.5 mg / week to 20 mg / week, 0.5 mg / week to 2 mg / week, 0.5 mg / week to 1.5 mg / week, 1 mg / week to 2 mg / week, 2 mg / week to 5 mg / week, 5 mg / week to 15 mg / week, 5 mg / week to 10 mg / week, 10 mg / week to 20 mg / week, 10 mg / week to 15 mg / week, 12 mg / week to 25 mg / week, 12 mg / week to 15 mg / week, 15 mg / week to 25 mg / week, 15 mg / week to 20 mg / week, or 20 mg / week to 25 mg / week. Clause 86. The method of any one of Clauses 47 to 85, wherein, upon administration to the subject, the composition produces an average concentration of the acylated peptide in serum of the subject within a range from 50 ng / mL to 500 ng / mL, 100 ng / mL to 300 ng / mL, or 150 ng / mL to 250 ng / mL. Clause 87. The method of any one of Clauses 47 to 86, wherein, upon administration to the subject, the composition produces a Cmaxof the acylated peptide in serum of the subject less than or equal to 2000 ng / mL. Clause 88. The method of any one of Clauses 47 to 87, wherein the composition is administered via subcutaneous injection. Clause 89. The method of any one of Clauses 47 to 88, wherein the disease or condition comprises diabetes or a diabetes-related condition. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 90. The method of Clause 89, wherein the diabetes or diabetes- related condition comprises prediabetes, type I diabetes, type II diabetes, hyperglycemia, or impaired glucose tolerance. Clause 91. The method of any one of Clauses 47 to 90, wherein the disease or condition comprises one or more of obesity, excessive body weight, an eating disorder, or obstructive sleep apnea. Clause 92. The method of any one of Clauses 47 to 91, wherein the disease or condition comprises one or more of the following: a cardiovascular disease, a liver disease, a neurological or neurodegenerative disease, an inflammatory disease, a renal disease, a bone disease, a hormonal disease, or a gastrointestinal disease. Clause 93. A composition for treating a disease or condition, the composition comprising: a dynamic hydrogel comprising a polymer and a plurality of nanoparticles, wherein the polymer is non-covalently crosslinked with the plurality of nanoparticles; and an incretin mimetic encapsulated by the dynamic hydrogel. Clause 94. The composition of Clause 93, wherein the incretin mimetic comprises a glucagon-like peptide-1 receptor agonist (GLP-1 RA). Clause 95. The composition of Clause 94, wherein the GLP-1 RA comprises exenatide, exenatide-LAR, lixisenatide, liraglutide, semaglutide, albiglutide, dulaglutide, efpeglenatide, ecnoglutide, efinopegdutide, cotadutide, mazdutide, BI 45690, tirzepatide, LY3493269, VK2735, CT-868, AMG133, or retatrutide. Clause 96. The composition of Clause 94, wherein the GLP-1 RA comprises liraglutide, semaglutide, ecnoglutide, cotadutide, mazdutide, tirzepatide, or retatrutide. Clause 97. The composition of any one of Clauses 94 to 96, wherein the GLP-1 RA comprises a peptide having a sequence with at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 99% sequence identity to any one of SEQ ID NO: 1 or SEQ ID NO: 2. Clause 98. The composition of any one of Clauses 93 to 97, wherein the incretin mimetic binds exclusively to a GLP-1 receptor. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 99. The composition of any one of Clauses 93 to 97, wherein the incretin mimetic binds to a GLP-1 receptor and at least one additional receptor. Clause 100. The composition of Clause 99, wherein the at least one additional receptor comprises one or more of a glucagon receptor or a gastric inhibitory peptide (GIP) receptor. Clause 101. The composition of any one of Clauses 93 to 100, wherein the incretin mimetic comprises an acylated peptide. Clause 102. The composition of Clause 101, wherein the acylated peptide includes a lipophilic substituent. Clause 103. The composition of Clause 102, wherein the acylated peptide is encapsulated in the dynamic hydrogel via interactions between the lipophilic substituent and the dynamic hydrogel. Clause 104. The composition of Clause 103, wherein the plurality of nanoparticles have hydrophobic surfaces that interact with the lipophilic substituent of the dynamic hydrogel. Clause 105. The composition of any one of Clauses 102 to 104, wherein the lipophilic substituent comprises an acyl group of a fatty acid. Clause 106. The composition of Clause 105, wherein the fatty acid is a C4 fatty acid, a C6 fatty acid, a C8 fatty acid, a C10 fatty acid, a C12 fatty acid, a C14 fatty acid, a C15 fatty acid, a C16 fatty acid, a C17 fatty acid, a C18 fatty acid, a C20 fatty acid, a C22 fatty acid, a C24 fatty acid, a C26 fatty acid, a C28 fatty acid, a C30 fatty acid, a C32 fatty acid, a C34 fatty acid, a C36 fatty acid, or a C38 fatty acid. Clause 107. The composition of any one of Clauses 102 to 106, further comprising a binding agent that interacts with the lipophilic substituent to physically entrap the acylated peptide in the dynamic hydrogel. Clause 108. The composition of Clause 107, wherein the binding agent comprises albumin. Clause 109. The composition of Clause 107 or 108, wherein the binding agent is larger than a mesh size of the dynamic hydrogel. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 110. The composition of any one of Clauses 101 to 109, wherein the acylated peptide is smaller than a mesh size of the dynamic hydrogel. Clause 111. The composition of any one of Clauses 101 to 110, further comprising a dispersing agent that inhibits aggregation of the acylated peptide. Clause 112. The composition of Clause 111, wherein the dispersing agent comprises one or more of a surfactant or a tonicity agent. Clause 113. The composition of Clause 112, wherein the dispersing agent comprises the surfactant, and the surfactant comprises one or more of a polysorbate, a sorbitan fatty acid ester, a poloxamer, a polyoxyethylene alkyl ether, an alkyl sulfate or a salt thereof, a fatty acid, a fatty acid alcohol, or a phospholipid. Clause 114. The composition of Clause 112 or 113, wherein the dispersing agent comprises the tonicity agent, and the tonicity agent comprises one or more of propylene glycol, glycerol, or mannitol. Clause 115. The composition of any one of Clauses 112 to 114, wherein a concentration of the dispersing agent in the composition is within a range from 0.1 mg / mL to 5 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, or 16 mg / mL to 26 mg / mL. Clause 116. The composition of any one of Clauses 93 to 100, wherein the incretin mimetic comprises a peptide conjugated to a protein or protein fragment. Clause 117. The composition of any one of Clauses 93 to 100, wherein the incretin mimetic comprises a peptide encapsulated in a microparticle. Clause 118. The composition of any one of Clauses 93 to 117, wherein the composition comprises from 1 mg to 250 mg of the incretin mimetic. Clause 119. The composition of any one of Clauses 93 to 118, wherein a concentration of the incretin mimetic in the composition is within a range from 1 mg / mL to 200 mg / mL. Clause 120. The composition of any one of Clauses 93 to 119, wherein the polymer comprises a hydrophobically-modified polysaccharide. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 121. The composition of Clause 120, wherein the hydrophobically- modified polysaccharide comprises a hydrophobically-modified cellulose derivative. Clause 122. The composition of Clause 121, wherein the hydrophobically- modified cellulose derivative is dodecyl-modified hydroxypropylmethylcellulose (HPMC- C12). Clause 123. The composition of any one of Clauses 93 to 122, wherein the plurality of nanoparticles comprise a plurality of polymeric nanoparticles. Clause 124. The composition of Clause 123, wherein the plurality of polymeric nanoparticles are amphiphilic. Clause 125. The composition of Clause 123 or 124, wherein the plurality of polymeric nanoparticles are poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) nanoparticles. Clause 126. The composition of any one of Clauses 93 to 125, wherein a concentration of the polymer in the dynamic hydrogel is within a range from 0.5 wt% to 5 wt%, 0.5 wt% to 4 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1 wt%, 1 wt% to 5 wt%, 1 wt% to 4 wt%, 1 wt% to 3 wt%, 1 wt% to 2 wt%, 2 wt% to 5 wt%, 2 wt% to 4 wt%, 2 wt% to 3 wt%, 3 wt% to 5 wt%, 3 wt% to 4 wt%, or 4 wt% to 5 wt%. Clause 127. The composition of any one of Clauses 93 to 126, wherein a concentration of the nanoparticles in the dynamic hydrogel is within a range from 1 wt% to 12 wt%, 1 wt% to 10 wt%, 1 wt% to 8 wt%, 1 wt% to 5 wt%, 1 wt% to 3 wt%, 3 wt% to 12 wt%, 3 wt% to 10 wt%, 3 wt% to 8 wt%, 3 wt% to 5 wt%, 5 wt % to 12 wt%, 5 wt% to 10 wt%, 5 wt% to 8 wt%, 8 wt% to 12 wt%, 8 wt% to 10 wt%, or 10 wt% to 12 wt%. Clause 128. The composition of any one of Clauses 93 to 127, wherein the dynamic hydrogel encapsulating the incretin mimetic has a storage modulus within a range from 10 Pa to 1000 Pa, or 50 Pa to 500 Pa when measured at 25 °C over an angular frequency of 0.1 rad / s to 100 rad / s within a linear viscoelastic region of the dynamic hydrogel. Clause 129. The composition of any one of Clauses 93 to 128, wherein the dynamic hydrogel encapsulating the incretin mimetic has a yield stress within a range from 1 Pa to 500 Pa, or 20 Pa to 200 Pa when measured at 25 °C. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 130. The composition of any one of Clauses 93 to 129, wherein the dynamic hydrogel encapsulating the incretin mimetic has a viscosity within a range from 100 mPa-s to 1000 mPa-s when measured at 25 °C at a shear rate of 1000 s-1. Clause 131. The composition of any one of Clauses 93 to 130, wherein, upon administration to a subject, the composition delivers the incretin mimetic to the subject over a treatment period of at least 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 28 days, 35 days, 40 days, 50 days, 60 days, 70 days, 80 days, 90 days, 100 days, 110 days, 120 days, 150 days, 180 days, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or 1 year. Clause 132. The composition of any one of Clauses 93 to 131, wherein, upon administration to a subject, the composition delivers the incretin mimetic at a rate to the subject within a range from 0.25 mg / week to 25 mg / week, 0.5 mg / week to 20 mg / week, 0.5 mg / week to 2 mg / week, 0.5 mg / week to 1.5 mg / week, 1 mg / week to 2 mg / week, 2 mg / week to 5 mg / week, 5 mg / week to 15 mg / week, 5 mg / week to 10 mg / week, 10 mg / week to 20 mg / week, 10 mg / week to 15 mg / week, 12 mg / week to 25 mg / week, 12 mg / week to 15 mg / week, 15 mg / week to 25 mg / week, 15 mg / week to 20 mg / week, or 20 mg / week to 25 mg / week. Clause 133. The composition of any one of Clauses 93 to 132, wherein, upon administration to a subject, the composition produces an average concentration of the incretin mimetic in serum of the subject within a range from 50 ng / mL to 500 ng / mL, 100 ng / mL to 300 ng / mL, or 150 ng / mL to 250 ng / mL. Clause 134. The composition of any one of Clauses 93 to 133, wherein, upon administration to a subject, the composition produces a Cmaxof the incretin mimetic in serum of the subject less than or equal to 2000 ng / mL. Clause 135. The composition of any one of Clauses 93 to 134, wherein the composition is configured for administration via subcutaneous injection. Clause 136. The composition of any one of Clauses 93 to 135, wherein the disease or condition comprises diabetes or a diabetes-related condition. Clause 137. The composition of Clause 136, wherein the diabetes or diabetes-related condition comprises prediabetes, type I diabetes, type II diabetes, hyperglycemia, or impaired glucose tolerance. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 138. The composition of any one of Clauses 93 to 137, wherein the disease or condition comprises one or more of obesity, excessive body weight, an eating disorder, or obstructive sleep apnea. Clause 139. The composition of any one of Clauses 93 to 138, wherein the disease or condition comprises one or more of the following: a cardiovascular disease, a liver disease, a neurological or neurodegenerative disease, an inflammatory disease, a renal disease, a bone disease, a hormonal disease, or a gastrointestinal disease. Clause 140. A method of treating a disease or condition, the method comprising: administering a composition to a subject, wherein the composition comprises: a dynamic hydrogel comprising a polymer and a plurality of nanoparticles, wherein the polymer is non-covalently crosslinked with the plurality of nanoparticles, and an incretin mimetic encapsulated by the dynamic hydrogel. Clause 141. The method of Clause 140, wherein the incretin mimetic comprises a glucagon-like peptide-1 receptor agonist (GLP-1 RA). Clause 142. The method of Clause 141, wherein the GLP-1 RA comprises exenatide, exenatide-LAR, lixisenatide, liraglutide, semaglutide, albiglutide, dulaglutide, efpeglenatide, ecnoglutide, efinopegdutide, cotadutide, mazdutide, BI 45690, tirzepatide, LY3493269, VK2735, CT-868, AMG133, or retatrutide. Clause 143. The method of Clause 141, wherein the GLP-1 RA comprises liraglutide, semaglutide, ecnoglutide, cotadutide, mazdutide, tirzepatide, or retatrutide. Clause 144. The method of any one of Clauses 140 to 143, wherein the GLP- 1 RA comprises a peptide having a sequence with at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 99% sequence identity to any one of SEQ ID NO: 1 or SEQ ID NO: 2. Clause 145. The method of any one of Clauses 140 to 144, wherein the incretin mimetic binds exclusively to a GLP-1 receptor. Clause 146. The method of any one of Clauses 140 to 144, wherein the incretin mimetic binds to a GLP-1 receptor and at least one additional receptor. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 147. The method of Clause 146, wherein the at least one additional receptor comprises one or more of a glucagon receptor or a gastric inhibitory peptide (GIP) receptor. Clause 148. The method of any one of Clauses 140 to 147, wherein the incretin mimetic comprises an acylated peptide. Clause 149. The method of Clause 148, wherein the acylated peptide includes a lipophilic substituent. Clause 150. The method of Clause 149, wherein the acylated peptide is encapsulated in the dynamic hydrogel via interactions between the lipophilic substituent and the dynamic hydrogel. Clause 151. The method of Clause 150, wherein the plurality of nanoparticles have hydrophobic surfaces that interact with the lipophilic substituent of the dynamic hydrogel. Clause 152. The method of any one of Clauses 149 to 151, wherein the lipophilic substituent comprises an acyl group of a fatty acid. Clause 153. The method of Clause 152, wherein the fatty acid is a C4 fatty acid, a C6 fatty acid, a C8 fatty acid, a C10 fatty acid, a C12 fatty acid, a C14 fatty acid, a C15 fatty acid, a C16 fatty acid, a C17 fatty acid, a C18 fatty acid, a C20 fatty acid, a C22 fatty acid, a C24 fatty acid, a C26 fatty acid, a C28 fatty acid, a C30 fatty acid, a C32 fatty acid, a C34 fatty acid, a C36 fatty acid, or a C38 fatty acid. Clause 154. The method of any one of Clauses 149 to 153, further comprising a binding agent that interacts with the lipophilic substituent to physically entrap the acylated peptide in the dynamic hydrogel. Clause 155. The method of Clause 154, wherein the binding agent comprises albumin. Clause 156. The method of Clause 154 or 155, wherein the binding agent is larger than a mesh size of the dynamic hydrogel. Clause 157. The method of any one of Clauses 148 to 156, wherein the acylated peptide is smaller than a mesh size of the dynamic hydrogel. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 158. The method of any one of Clauses 148 to 157, further comprising a dispersing agent that inhibits aggregation of the acylated peptide. Clause 159. The method of Clause 158, wherein the dispersing agent comprises one or more of a surfactant or a tonicity agent. Clause 160. The method of Clause 159, wherein the dispersing agent comprises the surfactant, and the surfactant comprises one or more of a polysorbate, a sorbitan fatty acid ester, a poloxamer, a polyoxyethylene alkyl ether, an alkyl sulfate or a salt thereof, a fatty acid, a fatty acid alcohol, or a phospholipid. Clause 161. The method of Clause 159 or 160, wherein the dispersing agent comprises the tonicity agent, and the tonicity agent comprises one or more of propylene glycol, glycerol, or mannitol. Clause 162. The method of any one of Clauses 159 to 161, wherein a concentration of the dispersing agent in the composition is within a range from 0.1 mg / mL to 5 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, or 16 mg / mL to 26 mg / mL. Clause 163. The method of any one of Clauses 140 to 147, wherein the incretin mimetic comprises a peptide conjugated to a protein or protein fragment. Clause 164. The method of any one of Clauses 140 to 147, wherein the incretin mimetic comprises a peptide encapsulated in a microparticle. Clause 165. The method of any one of Clauses 140 to 164, wherein the composition comprises from 1 mg to 250 mg of the incretin mimetic. Clause 166. The method of any one of Clauses 140 to 165, wherein a concentration of the incretin mimetic in the composition is within a range from 1 mg / mL to 200 mg / mL. Clause 167. The method of any one of Clauses 140 to 166, wherein the polymer comprises a hydrophobically-modified polysaccharide. Clause 168. The method of Clause 167, wherein the hydrophobically- modified polysaccharide comprises a hydrophobically-modified cellulose derivative. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 169. The method of Clause 168, wherein the hydrophobically- modified cellulose derivative is dodecyl-modified hydroxypropylmethylcellulose (HPMC- C12). Clause 170. The method of any one of Clauses 140 to 169, wherein the plurality of nanoparticles comprise a plurality of polymeric nanoparticles. Clause 171. The method of Clause 170, wherein the plurality of polymeric nanoparticles are amphiphilic. Clause 172. The method of Clause 170 or 171, wherein the plurality of polymeric nanoparticles are poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) nanoparticles. Clause 173. The method of any one of Clauses 140 to 172, wherein a concentration of the polymer in the dynamic hydrogel is within a range from 0.5 wt% to 5 wt%, 0.5 wt% to 4 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1 wt%, 1 wt% to 5 wt%, 1 wt% to 4 wt%, 1 wt% to 3 wt%, 1 wt% to 2 wt%, 2 wt% to 5 wt%, 2 wt% to 4 wt%, 2 wt% to 3 wt%, 3 wt% to 5 wt%, 3 wt% to 4 wt%, or 4 wt% to 5 wt%. Clause 174. The method of any one of Clauses 140 to 173, wherein a concentration of the nanoparticles in the dynamic hydrogel is within a range from 1 wt% to 12 wt%, 1 wt% to 10 wt%, 1 wt% to 8 wt%, 1 wt% to 5 wt%, 1 wt% to 3 wt%, 3 wt% to 12 wt%, 3 wt% to 10 wt%, 3 wt% to 8 wt%, 3 wt% to 5 wt%, 5 wt % to 12 wt%, 5 wt% to 10 wt%, 5 wt% to 8 wt%, 8 wt% to 12 wt%, 8 wt% to 10 wt%, or 10 wt% to 12 wt%. Clause 175. The method of any one of Clauses 140 to 174, wherein the dynamic hydrogel encapsulating the incretin mimetic has a storage modulus within a range from 10 Pa to 1000 Pa, or 50 Pa to 500 Pa when measured at 25 °C over an angular frequency of 0.1 rad / s to 100 rad / s within a linear viscoelastic region of the dynamic hydrogel. Clause 176. The method of any one of Clauses 140 to 175, wherein the dynamic hydrogel encapsulating the incretin mimetic has a yield stress within a range from 1 Pa to 500 Pa, or 20 Pa to 200 Pa when measured at 25 °C. Clause 177. The method of any one of Clauses 140 to 176, wherein the dynamic hydrogel encapsulating the incretin mimetic has a viscosity within a range from 100 mPa-s to 1000 mPa-s when measured at 25 °C at a shear rate of 1000 s-1. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 178. The method of any one of Clauses 140 to 177, wherein, upon administration to the subject, the composition delivers the incretin mimetic to the subject over a treatment period of at least 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 28 days, 35 days, 40 days, 50 days, 60 days, 70 days, 80 days, 90 days, 100 days, 110 days, 120 days, 150 days, 180 days, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or 1 year. Clause 179. The method of any one of Clauses 140 to 178, wherein, upon administration to the subject, the composition delivers the incretin mimetic at a rate to the subject within a range from 0.25 mg / week to 25 mg / week, 0.5 mg / week to 20 mg / week, 0.5 mg / week to 2 mg / week, 0.5 mg / week to 1.5 mg / week, 1 mg / week to 2 mg / week, 2 mg / week to 5 mg / week, 5 mg / week to 15 mg / week, 5 mg / week to 10 mg / week, 10 mg / week to 20 mg / week, 10 mg / week to 15 mg / week, 12 mg / week to 25 mg / week, 12 mg / week to 15 mg / week, 15 mg / week to 25 mg / week, 15 mg / week to 20 mg / week, or 20 mg / week to 25 mg / week. Clause 180. The method of any one of Clauses 140 to 179, wherein, upon administration to the subject, the composition produces an average concentration of the incretin mimetic in serum of the subject within a range from 50 ng / mL to 500 ng / mL, 100 ng / mL to 300 ng / mL, or 150 ng / mL to 250 ng / mL. Clause 181. The method of any one of Clauses 140 to 180, wherein, upon administration to the subject, the composition produces a Cmax of the incretin mimetic in serum of the subject less than or equal to 2000 ng / mL. Clause 182. The method of any one of Clauses 140 to 181, wherein the composition is administered via subcutaneous injection. Clause 183. The method of any one of Clauses 140 to 182, wherein the disease or condition comprises diabetes or a diabetes-related condition. Clause 184. The method of Clause 183, wherein the diabetes or diabetes- related condition comprises prediabetes, type I diabetes, type II diabetes, hyperglycemia, or impaired glucose tolerance. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO Clause 185. The method of any one of Clauses 140 to 184, wherein the disease or condition comprises one or more of obesity, excessive body weight, an eating disorder, or obstructive sleep apnea. Clause 186. The method of any one of Clauses 140 to 185, wherein the disease or condition comprises one or more of the following: a cardiovascular disease, a liver disease, a neurological or neurodegenerative disease, an inflammatory disease, a renal disease, a bone disease, a hormonal disease, or a gastrointestinal disease. Conclusion Although many of the embodiments are described above with respect to compositions and methods for delivery of incretin mimetics, the technology is applicable to other applications and / or other approaches, such as delivery of other types of therapeutic peptides. Moreover, other embodiments in addition to those described herein are within the scope of the technology. Additionally, several other embodiments of the technology can have different configurations, components, or procedures than those described herein. A person of ordinary skill in the art, therefore, will accordingly understand that the technology can have other embodiments with additional elements, or the technology can have other embodiments without several of the features shown and described above with reference to FIGS.1A–17. The descriptions of embodiments of the technology are not intended to be exhaustive or to limit the technology to the precise form disclosed above. Where the context permits, singular or plural terms may also include the plural or singular term, respectively. Although specific embodiments of, and examples for, the technology are described above for illustrative purposes, various equivalent modifications are possible within the scope of the technology, as those skilled in the relevant art will recognize. For example, while steps are presented in a given order, alternative embodiments may perform steps in a different order. The various embodiments described herein may also be combined to provide further embodiments. As used herein, the terms “generally,” “substantially,” “about,” and similar terms are used as terms of approximation and not as terms of degree, and are intended to account for the inherent variations in measured or calculated values that would be recognized by those of ordinary skill in the art. As used herein, the terms “about” and “approximately,” in reference to a number, may include numbers that fall within a range of 10%, 5%, or 1% in Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO either direction (greater than or less than) the number unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value). Moreover, unless the word “or” is expressly limited to mean only a single item exclusive from the other items in reference to a list of two or more items, then the use of “or” in such a list is to be interpreted as including (a) any single item in the list, (b) all of the items in the list, or (c) any combination of the items in the list. As used herein, the phrase “and / or” as in “A and / or B” refers to A alone, B alone, and A and B. Additionally, the term “comprising” is used throughout to mean including at least the recited feature(s) such that any greater number of the same feature and / or additional types of other features are not precluded. As used herein, the term “subject” may refer to any animal, including but not limited to, humans and non-human animals (e.g., dogs, cats, cows, horses, sheep, pigs, poultry, fish, crustaceans, etc.). As used herein, the term percent “identity,” in the context of two or more nucleic acid or polypeptide sequences, may refer to two or more sequences or subsequences that have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned for maximum correspondence, as measured using one of the sequence comparison algorithms described below (e.g., BLASTP and BLASTN or other algorithms available to persons of skill) or by visual inspection. Depending on the application, the percent “identity” can exist over a region of the sequence being compared, e.g., over a functional domain, or, alternatively, exist over the full length of the two sequences to be compared. For sequence comparison, typically one sequence acts as a reference sequence to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. For purposes herein, percent identity and sequence similarity may be performed using the BLAST algorithm, which is described in Altschul et al. (J. Mol. Biol. 215:403-410 (1990)). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. To the extent any materials incorporated herein by reference conflict with the present disclosure, the present disclosure controls. Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO It will also be appreciated that specific embodiments have been described herein for purposes of illustration, but that various modifications may be made without deviating from the technology. Further, while advantages associated with certain embodiments of the technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the technology. Accordingly, the disclosure and associated technology can encompass other embodiments not expressly shown or described herein.
Claims
Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO CLAIMS I / We claim:
1. A composition for treating a disease or condition, the composition comprising: a dynamic hydrogel comprising a polymer and a plurality of nanoparticles, wherein the polymer is non-covalently crosslinked with the plurality of nanoparticles; and an acylated peptide encapsulated by the dynamic hydrogel.
2. The composition of claim 1, wherein the acylated peptide includes a lipophilic substituent.
3. The composition of claim 2, wherein the acylated peptide is encapsulated in the dynamic hydrogel via interactions between the lipophilic substituent and the dynamic hydrogel.
4. The composition of claim 3, wherein the plurality of nanoparticles have hydrophobic surfaces that interact with the lipophilic substituent of the dynamic hydrogel.
5. The composition of any one of claims 2 to 4, wherein the lipophilic substituent comprises an acyl group of a fatty acid.
6. The composition of claim 5, wherein the fatty acid is a C4 fatty acid, a C6 fatty acid, a C8 fatty acid, a C10 fatty acid, a C12 fatty acid, a C14 fatty acid, a C15 fatty acid, a C16 fatty acid, a C17 fatty acid, a C18 fatty acid, a C20 fatty acid, a C22 fatty acid, a C24 fatty acid, a C26 fatty acid, a C28 fatty acid, a C30 fatty acid, a C32 fatty acid, a C34 fatty acid, a C36 fatty acid, or a C38 fatty acid.
7. The composition of any one of claims 2 to 6, further comprising a binding agent that interacts with the lipophilic substituent to physically entrap the acylated peptide in the dynamic hydrogel.
8. The composition of claim 7, wherein the binding agent comprises albumin.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 9. The composition of claim 7 or 8, wherein the binding agent is larger than a mesh size of the dynamic hydrogel.
10. The composition of any one of claims 1 to 9, wherein the acylated peptide is smaller than a mesh size of the dynamic hydrogel.
11. The composition of any one of claims 1 to 10, further comprising a dispersing agent that inhibits aggregation of the acylated peptide.
12. The composition of claim 11, wherein the dispersing agent comprises one or more of a surfactant or a tonicity agent.
13. The composition of claim 12, wherein the dispersing agent comprises the surfactant, and the surfactant comprises one or more of a polysorbate, a sorbitan fatty acid ester, a poloxamer, a polyoxyethylene alkyl ether, an alkyl sulfate, a fatty acid, a fatty acid alcohol, or a phospholipid.
14. The composition of claim 12 or 13, wherein the dispersing agent comprises the tonicity agent, and the tonicity agent comprises one or more of propylene glycol, glycerol, or mannitol.
15. The composition of any one of claims 12 to 14, wherein a concentration of the dispersing agent in the composition is within a range from 0.1 mg / mL to 5 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, or 16 mg / mL to 26 mg / mL.
16. The composition of any one of claims 1 to 15, wherein the acylated peptide comprises an incretin mimetic.
17. The composition of claim 16, wherein the incretin mimetic comprises a glucagon-like peptide-1 receptor agonist (GLP-1 RA).Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 18. The composition of claim 17, wherein the GLP-1 RA comprises one or more of liraglutide, semaglutide, ecnoglutide, cotadutide, mazdutide, tirzepatide, or retatrutide.
19. The composition of any one of claims 16 to 18, wherein the incretin mimetic binds exclusively to a GLP-1 receptor.
20. The composition of any one of claims 16 to 18, wherein the incretin mimetic binds to a GLP-1 receptor and at least one additional receptor.
21. The composition of claim 20, wherein the at least one additional receptor comprises one or more of a glucagon receptor or a gastric inhibitory peptide (GIP) receptor.
22. The composition of any one of claims 1 to 15, wherein the acylated peptide comprises an analogue of a proglucagon-derived peptide. The composition of any one of claims 1 to 15, wherein the acylated peptide comprises an amylin analogue. The composition of any one of claims 1 to 15, wherein the acylated peptide comprises an insulin analogue.
25. The composition of any one of claims 1 to 24, wherein the composition comprises from 1 mg to 250 mg of the acylated peptide.
26. The composition of any one of claims 1 to 25, wherein a concentration of the acylated peptide in the composition is within a range from 1 mg / mL to 200 mg / mL.
27. The composition of any one of claims 1 to 26, wherein the polymer comprises a hydrophobically-modified polysaccharide.
28. The composition of claim 27, wherein the hydrophobically-modified polysaccharide comprises a hydrophobically-modified cellulose derivative.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 29. The composition of claim 28, wherein the hydrophobically-modified cellulose derivative is dodecyl-modified hydroxypropylmethylcellulose (HPMC-C12).
30. The composition of any one of claims 1 to 29, wherein the plurality of nanoparticles comprise a plurality of polymeric nanoparticles.
31. The composition of claim 30, wherein the plurality of polymeric nanoparticles are amphiphilic.
32. The composition of claim 30 or 31, wherein the plurality of polymeric nanoparticles are poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) nanoparticles.
33. The composition of any one of claims 1 to 32, wherein a concentration of the polymer in the dynamic hydrogel is within a range from 0.5 wt% to 5 wt%, 0.5 wt% to 4 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1 wt%, 1 wt% to 5 wt%, 1 wt% to 4 wt%, 1 wt% to 3 wt%, 1 wt% to 2 wt%, 2 wt% to 5 wt%, 2 wt% to 4 wt%, 2 wt% to 3 wt%, 3 wt% to 5 wt%, 3 wt% to 4 wt%, or 4 wt% to 5 wt%.
34. The composition of any one of claims 1 to 33, wherein a concentration of the nanoparticles in the dynamic hydrogel is within a range from 1 wt% to 12 wt%, 1 wt% to 10 wt%, 1 wt% to 8 wt%, 1 wt% to 5 wt%, 1 wt% to 3 wt%, 3 wt% to 12 wt%, 3 wt% to 10 wt%, 3 wt% to 8 wt%, 3 wt% to 5 wt%, 5 wt % to 12 wt%, 5 wt% to 10 wt%, 5 wt% to 8 wt%, 8 wt% to 12 wt%, 8 wt% to 10 wt%, or 10 wt% to 12 wt%.
35. The composition of any one of claims 1 to 34, wherein the dynamic hydrogel encapsulating the acylated peptide has a storage modulus within a range from 10 Pa to 1000 Pa, or 50 Pa to 500 Pa when measured at 25 °C over an angular frequency of 0.1 rad / s to 100 rad / s within a linear viscoelastic region of the dynamic hydrogel.
36. The composition of any one of claims 1 to 35, wherein the dynamic hydrogel encapsulating the acylated peptide has a yield stress within a range from 1 Pa to 500 Pa, or 20 Pa to 200 Pa when measured at 25 °C.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 37. The composition of any one of claims 1 to 36, wherein the dynamic hydrogel encapsulating the acylated peptide has a viscosity within a range from 100 mPa-s to 1000 mPa- s when measured at 25 °C at a shear rate of 1000 s-1.
38. The composition of any one of claims 1 to 37, wherein, upon administration to a subject, the composition delivers the acylated peptide to the subject over a treatment period of at least 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 28 days, 35 days, 40 days, 50 days, 60 days, 70 days, 80 days, 90 days, 100 days, 110 days, 120 days, 150 days, 180 days, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or 1 year.
39. The composition of any one of claims 1 to 38, wherein, upon administration to a subject, the composition delivers the acylated peptide at a rate to the subject within a range from 0.25 mg / week to 25 mg / week, 0.5 mg / week to 20 mg / week, 0.5 mg / week to 2 mg / week, 0.5 mg / week to 1.5 mg / week, 1 mg / week to 2 mg / week, 2 mg / week to 5 mg / week, 5 mg / week to 15 mg / week, 5 mg / week to 10 mg / week, 10 mg / week to 20 mg / week, 10 mg / week to 15 mg / week, 12 mg / week to 25 mg / week, 12 mg / week to 15 mg / week, 15 mg / week to 25 mg / week, 15 mg / week to 20 mg / week, or 20 mg / week to 25 mg / week.
40. The composition of any one of claims 1 to 39, wherein, upon administration to a subject, the composition produces an average concentration of the acylated peptide in serum of the subject within a range from 50 ng / mL to 500 ng / mL, 100 ng / mL to 300 ng / mL, or 150 ng / mL to 250 ng / mL.
41. The composition of any one of claims 1 to 40, wherein, upon administration to a subject, the composition produces a Cmax of the acylated peptide in serum of the subject less than or equal to 2000 ng / mL.
42. The composition of any one of claims 1 to 41, wherein the composition is configured for administration via subcutaneous injection.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 43. The composition of any one of claims 1 to 42, wherein the disease or condition comprises diabetes or a diabetes-related condition.
44. The composition of claim 43, wherein the diabetes or diabetes-related condition comprises prediabetes, type I diabetes, type II diabetes, hyperglycemia, or impaired glucose tolerance.
45. The composition of any one of claims 1 to 44, wherein the disease or condition comprises one or more of obesity, excessive body weight, an eating disorder, or obstructive sleep apnea.
46. The composition of any one of claims 1 to 45, wherein the disease or condition comprises one or more of the following: a cardiovascular disease, a liver disease, a neurological or neurodegenerative disease, an inflammatory disease, a renal disease, a bone disease, a hormonal disease, or a gastrointestinal disease.
47. A method of treating a disease or condition, the method comprising: administering a composition to a subject, wherein the composition comprises: a dynamic hydrogel comprising a polymer and a plurality of nanoparticles, wherein the polymer is non-covalently crosslinked with the plurality of nanoparticles, and an acylated peptide encapsulated by the dynamic hydrogel.
48. The method of claim 47, wherein the acylated peptide includes a lipophilic substituent.
49. The method of claim 48, wherein the acylated peptide is encapsulated in the dynamic hydrogel via interactions between the lipophilic substituent and the dynamic hydrogel.
50. The method of claim 49, wherein the plurality of nanoparticles have hydrophobic surfaces that interact with the lipophilic substituent of the dynamic hydrogel.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 51. The method of any one of claims 48 to 50, wherein the lipophilic substituent comprises an acyl group of a fatty acid.
52. The method of claim 51, wherein the fatty acid is a C4 fatty acid, a C6 fatty acid, a C8 fatty acid, a C10 fatty acid, a C12 fatty acid, a C14 fatty acid, a C15 fatty acid, a C16 fatty acid, a C17 fatty acid, a C18 fatty acid, a C20 fatty acid, a C22 fatty acid, a C24 fatty acid, a C26 fatty acid, a C28 fatty acid, a C30 fatty acid, a C32 fatty acid, a C34 fatty acid, a C36 fatty acid, or a C38 fatty acid.
53. The method of any one of claims 48 to 52, further comprising a binding agent that interacts with the lipophilic substituent to physically entrap the acylated peptide in the dynamic hydrogel.
54. The method of claim 53, wherein the binding agent comprises albumin.
55. The composition of claim 53 or 54, wherein the binding agent is larger than a mesh size of the dynamic hydrogel.
56. The method of any one of claims 47 to 55, wherein the acylated peptide is smaller than a mesh size of the dynamic hydrogel.
57. The method of any one of claims 47 to 56, further comprising a dispersing agent that inhibits aggregation of the acylated peptide.
58. The method of claim 57, wherein the dispersing agent comprises one or more of a surfactant or a tonicity agent.
59. The method of claim 58, wherein the dispersing agent comprises the surfactant, and the surfactant comprises one or more of a polysorbate, a sorbitan fatty acid ester, a poloxamer, a polyoxyethylene alkyl ether, an alkyl sulfate or a salt thereof, a fatty acid, a fatty acid alcohol.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 60. The method of claim 58 or 59, wherein the dispersing agent comprises the tonicity agent, and the tonicity agent comprises one or more of propylene glycol, glycerol, or mannitol.
61. The method of any one of claims 58 to 60, wherein a concentration of the dispersing agent in the composition is within a range from 0.1 mg / mL to 5 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, or 16 mg / mL to 26 mg / mL.
62. The method of any one of claims 47 to 61, wherein the acylated peptide comprises an incretin mimetic.
63. The method of claim 62, wherein the incretin mimetic comprises a glucagon- like peptide-1 receptor agonist (GLP-1 RA).
64. The method of claim 63, wherein the GLP-1 RA comprises one or more of liraglutide, semaglutide, ecnoglutide, cotadutide, mazdutide, tirzepatide, or retatrutide.
65. The method of any one of claims 62 to 64, wherein the incretin mimetic binds exclusively to a GLP-1 receptor.
66. The method of any one of claims 62 to 64, wherein the incretin mimetic binds to a GLP-1 receptor and at least one additional receptor.
67. The method of claim 66, wherein the at least one additional receptor comprises one or more of a glucagon receptor or a gastric inhibitory peptide (GIP) receptor.
68. The method of any one of claims 47 to 67, wherein the acylated peptide comprises an analogue of a proglucagon-derived peptide.
69. The method of any one of claims 47 to 67, wherein the acylated peptide comprises an amylin analogue.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 70. The method of any one of claims 47-67 or 69, wherein the acylated peptide comprises an insulin analogue.
71. The method of any one of claims 47 to 70, wherein the composition comprises from 1 mg to 250 mg of the acylated peptide.
72. The method of any one of claims 47 to 71, wherein a concentration of the acylated peptide in the composition is within a range from 1 mg / mL to 200 mg / mL.
73. The method of any one of claims 47 to 72, wherein the polymer comprises a hydrophobically-modified polysaccharide.
74. The method of claim 73, wherein the hydrophobically-modified polysaccharide comprises a hydrophobically-modified cellulose derivative.
75. The method of claim 74, wherein the hydrophobically-modified cellulose derivative is dodecyl-modified hydroxypropylmethylcellulose (HPMC-C12).
76. The method of any one of claims 47 to 75, wherein the plurality of nanoparticles comprise a plurality of polymeric nanoparticles.
77. The method of claim 76, wherein the plurality of polymeric nanoparticles are amphiphilic.
78. The method of claim 76 or 77, wherein the plurality of polymeric nanoparticles are poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) nanoparticles.
79. The method of any one of claims 47 to 78, wherein a concentration of the polymer in the dynamic hydrogel is within a range from 0.5 wt% to 5 wt%, 0.5 wt% to 4 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1 wt%, 1 wt% to 5 wt%, 1 wt% to 4 wt%, 1 wt% to 3 wt%, 1 wt% to 2 wt%, 2 wt% to 5 wt%, 2 wt% to 4 wt%, 2 wt% to 3 wt%, 3 wt% to 5 wt%, 3 wt% to 4 wt%, or 4 wt% to 5 wt%.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 80. The method of any one of claims 47 to 79, wherein a concentration of the nanoparticles in the dynamic hydrogel is within a range from 1 wt% to 12 wt%, 1 wt% to 10 wt%, 1 wt% to 8 wt%, 1 wt% to 5 wt%, 1 wt% to 3 wt%, 3 wt% to 12 wt%, 3 wt% to 10 wt%, 3 wt% to 8 wt%, 3 wt% to 5 wt%, 5 wt % to 12 wt%, 5 wt% to 10 wt%, 5 wt% to 8 wt%, 8 wt% to 12 wt%, 8 wt% to 10 wt%, or 10 wt% to 12 wt%.
81. The method of any one of claims 47 to 80, wherein the dynamic hydrogel encapsulating the acylated peptide has a storage modulus within a range from 10 Pa to 1000 Pa, or 50 Pa to 500 Pa when measured at 25 °C over an angular frequency of 0.1 rad / s to 100 rad / s within a linear viscoelastic region of the dynamic hydrogel.
82. The method of any one of claims 47 to 81, wherein the dynamic hydrogel encapsulating the acylated peptide has a yield stress within a range from 1 Pa to 500 Pa, or 20 Pa to 200 Pa when measured at 25 °C.
83. The method of any one of claims 47 to 82, wherein the dynamic hydrogel encapsulating the acylated peptide has a viscosity within a range from 100 mPa-s to 1000 mPa- s when measured at 25 °C at a shear rate of 1000 s-1.
84. The method of any one of claims 47 to 83, wherein, upon administration to the subject, the composition delivers the acylated peptide to the subject over a treatment period of at least 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 28 days, 35 days, 40 days, 50 days, 60 days, 70 days, 80 days, 90 days, 100 days, 110 days, 120 days, 150 days, 180 days, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or 1 year.
85. The method of any one of claims 47 to 84, wherein, upon administration to the subject, the composition delivers the acylated peptide at a rate to the subject within a range from 0.25 mg / week to 25 mg / week, 0.5 mg / week to 20 mg / week, 0.5 mg / week to 2 mg / week, 0.5 mg / week to 1.5 mg / week, 1 mg / week to 2 mg / week, 2 mg / week to 5 mg / week, 5 mg / week to 15 mg / week, 5 mg / week to 10 mg / week, 10 mg / week to 20 mg / week, 10 mg / week to 15 mg / week, 12 mg / week to 25 mg / week, 12 mg / week to 15 mg / week, 15 mg / week to 25Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO mg / week, 15 mg / week to 20 mg / week, or 20 mg / week to 25 mg / week.
86. The method of any one of claims 47 to 85, wherein, upon administration to the subject, the composition produces an average concentration of the acylated peptide in serum of the subject within a range from 50 ng / mL to 500 ng / mL, 100 ng / mL to 300 ng / mL, or 150 ng / mL to 250 ng / mL.
87. The method of any one of claims 47 to 86, wherein, upon administration to the subject, the composition produces a Cmax of the acylated peptide in serum of the subject less than or equal to 2000 ng / mL.
88. The method of any one of claims 47 to 87, wherein the composition is administered via subcutaneous injection.
89. The method of any one of claims 47 to 88, wherein the disease or condition comprises diabetes or a diabetes-related condition.
90. The method of claim 89, wherein the diabetes or diabetes-related condition comprises prediabetes, type I diabetes, type II diabetes, hyperglycemia, or impaired glucose tolerance.
91. The method of any one of claims 47 to 90, wherein the disease or condition comprises one or more of obesity, excessive body weight, an eating disorder, or obstructive sleep apnea.
92. The method of any one of claims 47 to 91, wherein the disease or condition comprises one or more of the following: a cardiovascular disease, a liver disease, a neurological or neurodegenerative disease, an inflammatory disease, a renal disease, a bone disease, a hormonal disease, or a gastrointestinal disease.
93. A composition for treating a disease or condition, the composition comprising: a dynamic hydrogel comprising a polymer and a plurality of nanoparticles, wherein thePatent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO polymer is non-covalently crosslinked with the plurality of nanoparticles; and an incretin mimetic encapsulated by the dynamic hydrogel.
94. The composition of claim 93, wherein the incretin mimetic comprises a glucagon-like peptide-1 receptor agonist (GLP-1 RA).
95. The composition of claim 94, wherein the GLP-1 RA comprises exenatide, exenatide-LAR, lixisenatide, liraglutide, semaglutide, albiglutide, dulaglutide, efpeglenatide, ecnoglutide, efinopegdutide, cotadutide, mazdutide, BI 45690, tirzepatide, LY3493269, VK2735, CT-868, AMG133, or retatrutide.
96. The composition of claim 94, wherein the GLP-1 RA comprises liraglutide, semaglutide, ecnoglutide, cotadutide, mazdutide, tirzepatide, or retatrutide.
97. The composition of any one of claims 94 to 96, wherein the GLP-1 RA comprises a peptide having a sequence with at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 99% sequence identity to any one of SEQ ID NO: 1 or SEQ ID NO:
2.
98. The composition of any one of claims 93 to 97, wherein the incretin mimetic binds exclusively to a GLP-1 receptor.
99. The composition of any one of claims 93 to 97, wherein the incretin mimetic binds to a GLP-1 receptor and at least one additional receptor.
100. The composition of claim 99, wherein the at least one additional receptor comprises one or more of a glucagon receptor or a gastric inhibitory peptide (GIP) receptor.
101. The composition of any one of claims 93 to 100, wherein the incretin mimetic comprises an acylated peptide.
102. The composition of claim 101, wherein the acylated peptide includes a lipophilic substituent.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 103. The composition of claim 102, wherein the acylated peptide is encapsulated in the dynamic hydrogel via interactions between the lipophilic substituent and the dynamic hydrogel.
104. The composition of claim 103, wherein the plurality of nanoparticles have hydrophobic surfaces that interact with the lipophilic substituent of the dynamic hydrogel.
105. The composition of any one of claims 102 to 104, wherein the lipophilic substituent comprises an acyl group of a fatty acid.
106. The composition of claim 105, wherein the fatty acid is a C4 fatty acid, a C6 fatty acid, a C8 fatty acid, a C10 fatty acid, a C12 fatty acid, a C14 fatty acid, a C15 fatty acid, a C16 fatty acid, a C17 fatty acid, a C18 fatty acid, a C20 fatty acid, a C22 fatty acid, a C24 fatty acid, a C26 fatty acid, a C28 fatty acid, a C30 fatty acid, a C32 fatty acid, a C34 fatty acid, a C36 fatty acid, or a C38 fatty acid.
107. The composition of any one of claims 102 to 106, further comprising a binding agent that interacts with the lipophilic substituent to physically entrap the acylated peptide in the dynamic hydrogel.
108. The composition of claim 107, wherein the binding agent comprises albumin.
109. The composition of claim 107 or 108, wherein the binding agent is larger than a mesh size of the dynamic hydrogel.
110. The composition of any one of claims 101 to 109, wherein the acylated peptide is smaller than a mesh size of the dynamic hydrogel.
111. The composition of any one of claims 101 to 110, further comprising a dispersing agent that inhibits aggregation of the acylated peptide.
112. The composition of claim 111, wherein the dispersing agent comprises one orPatent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO more of a surfactant or a tonicity agent.
113. The composition of claim 112, wherein the dispersing agent comprises the surfactant, and the surfactant comprises one or more of a polysorbate, a sorbitan fatty acid ester, a poloxamer, a polyoxyethylene alkyl ether, an alkyl sulfate or a salt thereof, a fatty acid, a fatty acid alcohol, or a phospholipid.
114. The composition of claim 112 or 113, wherein the dispersing agent comprises the tonicity agent, and the tonicity agent comprises one or more of propylene glycol, glycerol, or mannitol.
115. The composition of any one of claims 112 to 114, wherein a concentration of the dispersing agent in the composition is within a range from 0.1 mg / mL to 5 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, or 16 mg / mL to 26 mg / mL.
116. The composition of any one of claims 93 to 100, wherein the incretin mimetic comprises a peptide conjugated to a protein or protein fragment.
117. The composition of any one of claims 93 to 100, wherein the incretin mimetic comprises a peptide encapsulated in a microparticle.
118. The composition of any one of claims 93 to 117, wherein the composition comprises from 1 mg to 250 mg of the incretin mimetic.
119. The composition of any one of claims 93 to 118, wherein a concentration of the incretin mimetic in the composition is within a range from 1 mg / mL to 200 mg / mL.
120. The composition of any one of claims 93 to 119, wherein the polymer comprises a hydrophobically-modified polysaccharide.
121. The composition of claim 120, wherein the hydrophobically-modifiedPatent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO polysaccharide comprises a hydrophobically-modified cellulose derivative.
122. The composition of claim 121, wherein the hydrophobically-modified cellulose derivative is dodecyl-modified hydroxypropylmethylcellulose (HPMC-C12).
123. The composition of any one of claims 93 to 122, wherein the plurality of nanoparticles comprise a plurality of polymeric nanoparticles.
124. The composition of claim 123, wherein the plurality of polymeric nanoparticles are amphiphilic.
125. The composition of claim 123 or 124, wherein the plurality of polymeric nanoparticles are poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) nanoparticles.
126. The composition of any one of claims 93 to 125, wherein a concentration of the polymer in the dynamic hydrogel is within a range from 0.5 wt% to 5 wt%, 0.5 wt% to 4 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1 wt%, 1 wt% to 5 wt%, 1 wt% to 4 wt%, 1 wt% to 3 wt%, 1 wt% to 2 wt%, 2 wt% to 5 wt%, 2 wt% to 4 wt%, 2 wt% to 3 wt%, 3 wt% to 5 wt%, 3 wt% to 4 wt%, or 4 wt% to 5 wt%.
127. The composition of any one of claims 93 to 126, wherein a concentration of the nanoparticles in the dynamic hydrogel is within a range from 1 wt% to 12 wt%, 1 wt% to 10 wt%, 1 wt% to 8 wt%, 1 wt% to 5 wt%, 1 wt% to 3 wt%, 3 wt% to 12 wt%, 3 wt% to 10 wt%, 3 wt% to 8 wt%, 3 wt% to 5 wt%, 5 wt % to 12 wt%, 5 wt% to 10 wt%, 5 wt% to 8 wt%, 8 wt% to 12 wt%, 8 wt% to 10 wt%, or 10 wt% to 12 wt%.
128. The composition of any one of claims 93 to 127, wherein the dynamic hydrogel encapsulating the incretin mimetic has a storage modulus within a range from 10 Pa to 1000 Pa, or 50 Pa to 500 Pa when measured at 25 °C over an angular frequency of 0.1 rad / s to 100 rad / s within a linear viscoelastic region of the dynamic hydrogel.
129. The composition of any one of claims 93 to 128, wherein the dynamic hydrogelPatent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO encapsulating the incretin mimetic has a yield stress within a range from 1 Pa to 500 Pa, or 20 Pa to 200 Pa when measured at 25 °C.
130. The composition of any one of claims 93 to 129, wherein the dynamic hydrogel encapsulating the incretin mimetic has a viscosity within a range from 100 mPa-s to 1000 mPa- s when measured at 25 °C at a shear rate of 1000 s-1.
131. The composition of any one of claims 93 to 130, wherein, upon administration to a subject, the composition delivers the incretin mimetic to the subject over a treatment period of at least 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 28 days, 35 days, 40 days, 50 days, 60 days, 70 days, 80 days, 90 days, 100 days, 110 days, 120 days, 150 days, 180 days, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or 1 year.
132. The composition of any one of claims 93 to 131, wherein, upon administration to a subject, the composition delivers the incretin mimetic at a rate to the subject within a range from 0.25 mg / week to 25 mg / week, 0.5 mg / week to 20 mg / week, 0.5 mg / week to 2 mg / week, 0.5 mg / week to 1.5 mg / week, 1 mg / week to 2 mg / week, 2 mg / week to 5 mg / week, 5 mg / week to 15 mg / week, 5 mg / week to 10 mg / week, 10 mg / week to 20 mg / week, 10 mg / week to 15 mg / week, 12 mg / week to 25 mg / week, 12 mg / week to 15 mg / week, 15 mg / week to 25 mg / week, 15 mg / week to 20 mg / week, or 20 mg / week to 25 mg / week.
133. The composition of any one of claims 93 to 132, wherein, upon administration to a subject, the composition produces an average concentration of the incretin mimetic in serum of the subject within a range from 50 ng / mL to 500 ng / mL, 100 ng / mL to 300 ng / mL, or 150 ng / mL to 250 ng / mL.
134. The composition of any one of claims 93 to 133, wherein, upon administration to a subject, the composition produces a Cmax of the incretin mimetic in serum of the subject less than or equal to 2000 ng / mL.
135. The composition of any one of claims 93 to 134, wherein the composition isPatent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO configured for administration via subcutaneous injection.
136. The composition of any one of claims 93 to 135, wherein the disease or condition comprises diabetes or a diabetes-related condition.
137. The composition of claim 136, wherein the diabetes or diabetes-related condition comprises prediabetes, type I diabetes, type II diabetes, hyperglycemia, or impaired glucose tolerance.
138. The composition of any one of claims 93 to 137, wherein the disease or condition comprises one or more of obesity, excessive body weight, an eating disorder, or obstructive sleep apnea.
139. The composition of any one of claims 93 to 138, wherein the disease or condition comprises one or more of the following: a cardiovascular disease, a liver disease, a neurological or neurodegenerative disease, an inflammatory disease, a renal disease, a bone disease, a hormonal disease, or a gastrointestinal disease.
140. A method of treating a disease or condition, the method comprising: administering a composition to a subject, wherein the composition comprises: a dynamic hydrogel comprising a polymer and a plurality of nanoparticles, wherein the polymer is non-covalently crosslinked with the plurality of nanoparticles, and an incretin mimetic encapsulated by the dynamic hydrogel.
141. The method of claim 140, wherein the incretin mimetic comprises a glucagon- like peptide-1 receptor agonist (GLP-1 RA).
142. The method of claim 141, wherein the GLP-1 RA comprises exenatide, exenatide-LAR, lixisenatide, liraglutide, semaglutide, albiglutide, dulaglutide, efpeglenatide, ecnoglutide, efinopegdutide, cotadutide, mazdutide, BI 45690, tirzepatide, LY3493269, VK2735, CT-868, AMG133, or retatrutide.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 143. The method of claim 141, wherein the GLP-1 RA comprises liraglutide, semaglutide, ecnoglutide, cotadutide, mazdutide, tirzepatide, or retatrutide.
144. The method of any one of claims 140 to 143, wherein the GLP-1 RA comprises a peptide having a sequence with at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, or 99% sequence identity to any one of SEQ ID NO: 1 or SEQ ID NO:
2.
145. The method of any one of claims 140 to 144, wherein the incretin mimetic binds exclusively to a GLP-1 receptor.
146. The method of any one of claims 140 to 144, wherein the incretin mimetic binds to a GLP-1 receptor and at least one additional receptor.
147. The method of claim 146, wherein the at least one additional receptor comprises one or more of a glucagon receptor or a gastric inhibitory peptide (GIP) receptor.
148. The method of any one of claims 140 to 147, wherein the incretin mimetic comprises an acylated peptide.
149. The method of claim 148, wherein the acylated peptide includes a lipophilic substituent.
150. The method of claim 149, wherein the acylated peptide is encapsulated in the dynamic hydrogel via interactions between the lipophilic substituent and the dynamic hydrogel.
151. The method of claim 150, wherein the plurality of nanoparticles have hydrophobic surfaces that interact with the lipophilic substituent of the dynamic hydrogel.
152. The method of any one of claims 149 to 151, wherein the lipophilic substituent comprises an acyl group of a fatty acid.
153. The method of claim 152, wherein the fatty acid is a C4 fatty acid, a C6 fattyPatent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO acid, a C8 fatty acid, a C10 fatty acid, a C12 fatty acid, a C14 fatty acid, a C15 fatty acid, a C16 fatty acid, a C17 fatty acid, a C18 fatty acid, a C20 fatty acid, a C22 fatty acid, a C24 fatty acid, a C26 fatty acid, a C28 fatty acid, a C30 fatty acid, a C32 fatty acid, a C34 fatty acid, a C36 fatty acid, or a C38 fatty acid.
154. The method of any one of claims 149 to 153, further comprising a binding agent that interacts with the lipophilic substituent to physically entrap the acylated peptide in the dynamic hydrogel.
155. The method of claim 154, wherein the binding agent comprises albumin.
156. The method of claim 154 or 155, wherein the binding agent is larger than a mesh size of the dynamic hydrogel.
157. The method of any one of claims 148 to 156, wherein the acylated peptide is smaller than a mesh size of the dynamic hydrogel.
158. The method of any one of claims 148 to 157, further comprising a dispersing agent that inhibits aggregation of the acylated peptide.
159. The method of claim 158, wherein the dispersing agent comprises one or more of a surfactant or a tonicity agent.
160. The method of claim 159, wherein the dispersing agent comprises the surfactant, and the surfactant comprises one or more of a polysorbate, a sorbitan fatty acid ester, a poloxamer, a polyoxyethylene alkyl ether, an alkyl sulfate or a salt thereof, a fatty acid, a fatty acid alcohol, or a phospholipid.
161. The method of claim 159 or 160, wherein the dispersing agent comprises the tonicity agent, and the tonicity agent comprises one or more of propylene glycol, glycerol, or mannitol.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 162. The method of any one of claims 159 to 161, wherein a concentration of the dispersing agent in the composition is within a range from 0.1 mg / mL to 5 mg / mL, 0.5 mg / mL to 1.5 mg / mL, 1 mg / mL to 2 mg / mL, 1 mg / mL to 50 mg / mL, 5 mg / mL to 40 mg / mL, 10 mg / mL to 30 mg / mL, or 16 mg / mL to 26 mg / mL.
163. The method of any one of claims 140 to 147, wherein the incretin mimetic comprises a peptide conjugated to a protein or protein fragment.
164. The method of any one of claims 140 to 147, wherein the incretin mimetic comprises a peptide encapsulated in a microparticle.
165. The method of any one of claims 140 to 164, wherein the composition comprises from 1 mg to 250 mg of the incretin mimetic.
166. The method of any one of claims 140 to 165, wherein a concentration of the incretin mimetic in the composition is within a range from 1 mg / mL to 200 mg / mL.
167. The method of any one of claims 140 to 166, wherein the polymer comprises a hydrophobically-modified polysaccharide.
168. The method of claim 167, wherein the hydrophobically-modified polysaccharide comprises a hydrophobically-modified cellulose derivative.
169. The method of claim 168, wherein the hydrophobically-modified cellulose derivative is dodecyl-modified hydroxypropylmethylcellulose (HPMC-C12).
170. The method of any one of claims 140 to 169, wherein the plurality of nanoparticles comprise a plurality of polymeric nanoparticles.
171. The method of claim 170, wherein the plurality of polymeric nanoparticles are amphiphilic.Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 172. The method of claim 170 or 171, wherein the plurality of polymeric nanoparticles are poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) nanoparticles.
173. The method of any one of claims 140 to 172, wherein a concentration of the polymer in the dynamic hydrogel is within a range from 0.5 wt% to 5 wt%, 0.5 wt% to 4 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1 wt%, 1 wt% to 5 wt%, 1 wt% to 4 wt%, 1 wt% to 3 wt%, 1 wt% to 2 wt%, 2 wt% to 5 wt%, 2 wt% to 4 wt%, 2 wt% to 3 wt%, 3 wt% to 5 wt%, 3 wt% to 4 wt%, or 4 wt% to 5 wt%.
174. The method of any one of claims 140 to 173, wherein a concentration of the nanoparticles in the dynamic hydrogel is within a range from 1 wt% to 12 wt%, 1 wt% to 10 wt%, 1 wt% to 8 wt%, 1 wt% to 5 wt%, 1 wt% to 3 wt%, 3 wt% to 12 wt%, 3 wt% to 10 wt%, 3 wt% to 8 wt%, 3 wt% to 5 wt%, 5 wt % to 12 wt%, 5 wt% to 10 wt%, 5 wt% to 8 wt%, 8 wt% to 12 wt%, 8 wt% to 10 wt%, or 10 wt% to 12 wt%.
175. The method of any one of claims 140 to 174, wherein the dynamic hydrogel encapsulating the incretin mimetic has a storage modulus within a range from 10 Pa to 1000 Pa, or 50 Pa to 500 Pa when measured at 25 °C over an angular frequency of 0.1 rad / s to 100 rad / s within a linear viscoelastic region of the dynamic hydrogel.
176. The method of any one of claims 140 to 175, wherein the dynamic hydrogel encapsulating the incretin mimetic has a yield stress within a range from 1 Pa to 500 Pa, or 20 Pa to 200 Pa when measured at 25 °C.
177. The method of any one of claims 140 to 176, wherein the dynamic hydrogel encapsulating the incretin mimetic has a viscosity within a range from 100 mPa-s to 1000 mPa- s when measured at 25 °C at a shear rate of 1000 s-1.
178. The method of any one of claims 140 to 177, wherein, upon administration to the subject, the composition delivers the incretin mimetic to the subject over a treatment period of at least 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 28 days, 35 days, 40 days, 50 days, 60 days, 70 days, 80 days, 90 days, 100 days, 110 days, 120 days, 150 days,Patent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO 180 days, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or 1 year.
179. The method of any one of claims 140 to 178, wherein, upon administration to the subject, the composition delivers the incretin mimetic at a rate to the subject within a range from 0.25 mg / week to 25 mg / week, 0.5 mg / week to 20 mg / week, 0.5 mg / week to 2 mg / week, 0.5 mg / week to 1.5 mg / week, 1 mg / week to 2 mg / week, 2 mg / week to 5 mg / week, 5 mg / week to 15 mg / week, 5 mg / week to 10 mg / week, 10 mg / week to 20 mg / week, 10 mg / week to 15 mg / week, 12 mg / week to 25 mg / week, 12 mg / week to 15 mg / week, 15 mg / week to 25 mg / week, 15 mg / week to 20 mg / week, or 20 mg / week to 25 mg / week.
180. The method of any one of claims 140 to 179, wherein, upon administration to the subject, the composition produces an average concentration of the incretin mimetic in serum of the subject within a range from 50 ng / mL to 500 ng / mL, 100 ng / mL to 300 ng / mL, or 150 ng / mL to 250 ng / mL.
181. The method of any one of claims 140 to 180, wherein, upon administration to the subject, the composition produces a Cmax of the incretin mimetic in serum of the subject less than or equal to 2000 ng / mL.
182. The method of any one of claims 140 to 181, wherein the composition is administered via subcutaneous injection.
183. The method of any one of claims 140 to 182, wherein the disease or condition comprises diabetes or a diabetes-related condition.
184. The method of claim 183, wherein the diabetes or diabetes-related condition comprises prediabetes, type I diabetes, type II diabetes, hyperglycemia, or impaired glucose tolerance.
185. The method of any one of claims 140 to 184, wherein the disease or condition comprises one or more of obesity, excessive body weight, an eating disorder, or obstructivePatent Attorney Docket No.: 079445-1451220-012910PC Client Ref.: S23-231 Fortem Ref.: APL.010WO sleep apnea.
186. The method of any one of claims 140 to 185, wherein the disease or condition comprises one or more of the following: a cardiovascular disease, a liver disease, a neurological or neurodegenerative disease, an inflammatory disease, a renal disease, a bone disease, a hormonal disease, or a gastrointestinal disease.