Structure–property relationships in ABC-type polymer carriers: exploring drug loading and release behavior via dissipative particle dynamics simulation

Polymeric drug delivery systems for long‑acting and injectable therapeutics: structure–property relationships, mechanisms, and translational consideration

Polymeric drug delivery systems have emerged as versatile platforms for achieving controlled and sustained therapeutic release. This review focuses on clinically relevant long‑acting injectable and implantable systems, including polymeric nanoparticles, microspheres, in situ forming depots, and implantable devices, with an emphasis on how polymer chemistry governs their performance. We examine the relationships between polymer structure – encompassing backbone chemistry, molecular weight, architecture, and functionalization – and emergent physicochemical properties such as hydrophobicity, mesh size, diffusivity, and degradation behavior. These properties collectively determine drug loading, release kinetics, and biological interactions.Mechanistic models, including diffusion‑controlled (Higuchi), anomalous transport (Korsmeyer–Peppas), and degradation‑driven kinetics, are discussed to provide a quantitative framework for understanding drug release behavior across different systems. Representative clinical products, such as PLGA‑based depots and implants, illustrate the translation of structure–property relationships into therapeutic function, while comparisons with emerging nanocarrier systems highlight distinct design trade‑offs between localized and systemic delivery approaches. In addition, ligand‑functionalized polymeric systems are evaluated with respect to receptor‑mediated targeting, intracellular trafficking, and biological barriers that influence in vivo performance.Despite significant advances, challenges remain in achieving predictable in vitro–in vivo correlations, minimizing variability in manufacturing, and improving targeting efficiency. By integrating molecular design, transport mechanisms, and translational considerations, this review provides a structured framework for the rational development of next‑generation polymer‑based drug delivery systems.

Modeling the effect of macromolecular architecture on phase behavior in A–B diblock copolymer/homopolymer C blends

Ionic Liquid-Integrated Interpenetrating Polymer Hydrogel for Injectable, Self-Healing, and Stimuli-Responsive Co-Delivery of Protein and Chemotherapeutic Agents in Breast Cancer Therapy.

Due to poor drug solubility, protein instability, and inefficient carrier systems, the co-delivery of chemotherapeutics and proteins remains a critical challenge in cancer therapy. To address these limitations, we developed a stimuli-responsive, multifunctional polymeric hydrogel by incorporating biocompatible choline-lineolate ([Cho][Lin]) ionic liquid into a sodium alginate (SA) and polyvinyl alcohol (PVA) matrix for enhanced co-delivery of doxorubicin (DOX) and zein in localized breast cancer treatment. Small-angle neutron scattering suggested the aggregation behavior of [Cho][Lin] and confirmed the solubility and stability of the drug and protein within the hydrogel. Fourier-transform infrared spectroscopy and circular dichroism demonstrated noncovalent interactions between the ionic liquid and polymers, alongside preserved protein structural integrity. Field-emission scanning electron microscopy revealed a well-defined, porous three-dimensional network with elongated fibers, while rheological analysis confirmed mechanical stability (γc = 100% strain), viscoelasticity, and shear-thinning behavior. The hydrogel exhibited self-healing, injectability, and strong adhesion, with in vitro biocompatibility assays on HaCaT cells showing >92% viability after 48 h. Drug and protein release studies demonstrated pH-responsive behavior, with significantly higher release under acidic conditions (89% DOX, 80% zein) than neutral pH. In vitro cytotoxicity assays on MCF-7 breast cancer cells revealed an IC50 of ∼2 μM for the drug-loaded hydrogel. These results highlight the potential of ionic liquid-based hydrogels as a versatile and practical platform for the co-delivery of therapeutic agents, offering a targeted and efficient strategy for localized breast cancer therapy.

Establishing Structure‐Property Relationships in Model Amphiphilic Polymer Co‐Networks

Amphiphilic polymer co‐networks (APCNs) offer a versatile platform as materials for numerous applications, yet their rational design requires a fundamental understanding of the complex interplay between molecular architecture and macroscopic properties. Here, we present a well‐defined model platform based on the heterocomplementary coupling of tetra‐PEG and tetra‐PCL star polymers. This system enables the systematic exploration of how synthesis conditions govern network formation, mechanical response, and transport behavior. Network properties were characterized through swelling studies and rheology, while the diffusion of star polymers was probed using combined Fluorescence Recovery After Photobleaching (FRAP) and Forced Rayleigh Scattering (FRS). Complementary Dynamic Light Scattering (DLS) experiments with diffusive probes enabled the extraction of diffusion‐governing length scales, such as the network correlation length and the hydrodynamic screening length. This multi‐methodological approach establishes quantitative structure–property–transport relationships and highlights the interplay between synthesis, network architecture, and functional properties. The PEG–PCL model APCN platform thus provides a predictive framework for the rational design of tailor‐made amphiphilic materials with tunable mechanics and transport characteristics.

Engineering PLGA Nanocomposite Matrices: Influence of Polymer Structure on Drug Release Kinetics and Ocular Pharmacokinetics

The study emphasizes the role of PLGA as a biodegradable polymeric matrix governing drug release through diffusion and polymer erosion mechanisms, thereby functioning as a polymer–drug nanocomposite system. The structural and physicochemical properties of the polymer matrix play a critical role in controlling drug encapsulation and release kinetics. The solvent evaporation technique was utilized to fabricate PLGA nanoparticles, and a 3² factorial design was implemented for optimization. The optimized combination exhibited a zeta potential of −21.5 ± 2.6 mV, a polydispersity index of 0.182 ± 0.03, and an average particle size of 178.6 ± 12.4 nm. The drug loading was determined to be 14.6 ± 1.2%, while the drug entrapment efficiency was found to be 82.3 ± 3.7%. The biphasic release pattern was demonstrated in in vitro release studies. The initial burst release transpired within 6 hours, with a release rate of 21.4 ± 2.1%. The second burst release transpired within 72 hours, yielding a cumulative release rate of 88.7 ± 3.5%. Investigations into the permeability of nanoparticles in goat corneas revealed a 1.97-fold enhancement in the permeability coefficient, with drug infiltration from nanoparticles significantly exceeding that from drug suspension (68.2 ± 4.3% versus 34.6 ± 3.1%; p < 0.001). In vivo research on the pharmacokinetics of medicine absorption and ocular residence time in New Zealand albino rabbits (n = 6) demonstrated that PLGA nanoparticles significantly enhanced both parameters. The nanoparticle formulation exhibited a peak drug concentration (C_max) of 3.84 ± 0.42 µg/mL in aqueous humor, whereas the suspension demonstrated a concentration of 1.76 ± 0.28 µg/mL (p < 0.001). The extended duration to achieve maximum concentration (T_max) (4.0 ± 0.5 h vs. 1.5 ± 0.3 h) indicates a sustained release pattern. The nanoparticles exhibited a 2.2-fold enhancement in bioavailability, evidenced by a much larger area under the curve (AUC₀-24h) of 28.6 ± 3.2 µg·h/mL, in contrast to the suspension's 12.9 ± 2.1 µg·h/mL. The results indicate that PLGA nanoparticles offer superior therapeutic efficacy, prolonged drug release, and improved bioavailability as a carrier system for sustained ocular delivery of dexamethasone. The study emphasizes how polymer matrix density, interfacial stabilization, and crystallinity govern diffusion pathways and degradation-controlled release.

Think Beyond The Core: Computationally Decoding the Hydrophilic Corona of Drug-Loaded Polymer Micelles.

Polymeric micelles are established delivery platforms for hydrophobic drugs. The molecular interactions governing their structure and function remain, however, poorly understood. All-atom molecular dynamics simulations are used to investigate drug-loaded ABA-type triblock copolymer micelles with a hydrophobic poly(2-n-butyl-2-oxazine) core and hydrophilic coronas composed of poly(ethylene glycol) (pEG), poly(N,N-dimethylacrylamide) (pDMAA), and poly(sarcosine) (pSAR). Here, pDMAA and pSAR are considered as alternative polymers to address emerging pEG immunogenicity. Three micellar formulations are examined at moderate (20%) and high (60%) loadings of curcumin as a model hydrophobic drug. The simulations reveal that pEG-based micelles exhibit higher hydration and looser corona structures compared to pDMAA and pSAR micelles. In pEG micelles, curcumin localizes primarily within the hydrophobic core, whereas in pDMAA and pSAR micelles it is more uniformly distributed. At both drug loadings, curcumin preferentially aggregates into a single stable cluster, not densely packed, and interpenetrated by polymer chains. Micelles with pDMAA and pSAR coronas exhibit enhanced stability, reflecting higher internal density and tighter curcumin packing. Hydrogen bond analysis reveals the strongest curcumin-hydrophilic A-block interactions in pDMAA micelles, moderate loading-dependent interactions in pSAR micelles, and minimal hydrogen-bonding in pEG micelles due to corona hydration.