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