Polymeric drug delivery systems for long‑acting and injectable therapeutics: structure–property relationships, mechanisms, and translational consideration
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.
Overall, this review shows that nanofiber-based drug delivery systems have significant advantages over conventional dosage forms and demonstrate considerable potential for next-generation therapies and pharmaceutical products with systematic formulation optimization, standardized characterization protocols, and clinically relevant evaluation strategies.
Prachi S. Patil, Pravin Pawar· Current Nanomaterials· 0 citations
The development of nanoparticle-based drug delivery systems represents a major step forward in pharmaceutical science, with the goal of enhancing treatment effectiveness while ensuring patient safety. Among these systems, polymeric nanoparticles-especially those made from biodegradable materials-have gained considerable interest due to their biocompatibility and versatile structural properties. Through careful formulation approaches, including surface modification, appropriate polymer selection, and optimization of physicochemical properties, these carriers can achieve sustained and controlled drug release. Such controlled release helps maintain stable drug levels in the bloodstream, reduces dosing frequency, and minimizes adverse effects. Furthermore, incorporating targeting strategies allows for more precise drug delivery by promoting accumulation at specific sites of action. In addition, advanced stimuli-responsive systems introduce an extra level of regulation, enabling drug release in response to specific biological triggers like pH changes, temperature variations, or enzymatic activity. This review highlights key design principles, explores mechanisms underlying controlled and targeted delivery, and discusses the growing importance of smart polymeric systems in the evolving field of nanomedicine.
Babitha Ms, Kamaleshwari Ms, P. Preetha et al.· International journal for de...· 0 citations
This review highlights a formulation-driven framework for the rational design and clinical translation of hydrogel-based pharmaceutical excipients in advanced drug delivery systems.
Suriya Prakaash Kannan, Dakshinesh Parameswaran, Damodharan Narayanasamy· Biochemical and Biophysical...· 0 citations
The interactive combination of physics‐based structural engineering and chemistry‐based functional modification offers an efficient framework for developing the next‐generation nanofiber‐based drug delivery systems.
Madhavi Porwal, Phool Chandra, S. Sridhar et al.· Polymers for Advanced Techno...· 0 citations
This review provides a comprehensive assessment of four major nanoparticle families—polymeric carriers, lipid-based vehicles, inorganic systems, inorganic systems, and hybrid composites—focusing on how their physicochemical properties govern drug encapsulation, release behavior, and tissue compatibility.
Z. Asiri, Abeer Mobarki, Sahar S. Alghamdi et al.· International Journal of Mol...· 0 citations
Peptides and proteins have become central to modern therapeutics because of their high biological specificity and ability to modulate targets that are often inaccessible to small molecules. However, their clinical use remains constrained by molecular instability, enzymatic degradation, rapid systemic clearance, poor epithelial permeability, immunogenicity risk, and the practical burden of repeated parenteral administration. Polymeric delivery systems offer versatile strategies to address these limitations through molecular conjugation, biodegradable depots, nanoparticles, micelles, hydrogels, nanogels, mucoadhesive systems, and microneedle-based platforms. This review summarizes the design principles, biological barriers, formulation challenges, and translational considerations that govern polymeric peptide and protein delivery. Particular emphasis is placed on polymer-cargo interactions, stability preservation, controlled release versus polymer degradation, critical quality attributes, safety, immunogenicity, manufacturability, and regulatory complexity. Clinically mature examples, including PEGylated proteins and PLGA/PLA-based long-acting depots, demonstrate that polymeric technologies can improve pharmacokinetics and dosing convenience when the delivery objective is clearly defined and product complexity remains manageable. In contrast, many nanoscale, mucosal, and stimuli-responsive systems remain limited by weak in vitro-in vivo translation, incomplete characterization of released cargo bioactivity, scale-up difficulty, and uncertain regulatory pathways. Future progress will require development strategies that begin with clinical need and target product profile rather than platform novelty alone. Successful polymeric systems are likely to be those that integrate protein stability, controlled exposure, patient usability, robust manufacturing, validated analytics, and regulatory clarity into a coherent product-development framework.
Ayman M. Al-Qaaneh, Mai S Khanfar· International journal of pha...· 1 citation