Polymeric drug delivery systems for long‑acting and injectable therapeutics: structure–property relationships, mechanisms, and translational consideration
Aug 2026· Nucleic Acid Insights· Vol 3, pp. 365–388· 0 citations
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.
Considering that nanofibers can precisely control drug loading, release kinetics, and therapeutic performance, they have become a highly attractive platform for improved drug delivery systems. Because it enables the production of continuous nanofibers with customizable designs, such as
core–shell, porous, aligned, and multi-component structures, electrospinning is the most commonly
used approach among the many fabrication methods. These structural characteristics allow for the
effective encapsulation of a wide range of medications and provide significant advantages in terms of
formulation versatility. High drug encapsulation efficiency, improved solubility and bioavailability
of poorly water-soluble drugs, and adaptable release patterns that can be customized for immediate,
sustained, or targeted delivery have all been repeatedly reported with electrospun nanofibers. Crucially, drug–polymer interactions, the physical stability of the loaded drug, and the predominant release mechanisms—such as diffusion, polymer degradation, or swelling-controlled transport—are all
directly impacted by nanoscale structural control. Furthermore, enhanced mass transfer and enhanced
contact with biological environments are made possible by nanofibers' high surface area-to-volume
ratio. Nanofibrous scaffolds are particularly appealing for tissue engineering and wound healing
applications because of their extracellular matrix-mimicking morphology, which improves cell adhesion, proliferation, and tissue integration in addition to medication administration. Overall, this review shows that nanofiber-based drug delivery systems have significant advantages over conventional dosage forms. They also demonstrate considerable potential for next-generation therapies and
pharmaceutical products with systematic formulation optimization, standardized characterization
protocols, and clinically relevant evaluation strategies. Furthermore, the incorporation of intelligent
and stimuli-responsive nanofibers could increase their usefulness for precision and personalized
therapy
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
OBJECTIVES
This review aims to provide a systematic overview of hydrogel systems as pharmaceutical excipients for drug delivery. It focuses on their classification, formulation strategies, physicochemical properties, and applicability across different routes of administration.
SIGNIFICANCE
Hydrogels have progressed into multifunctional excipients capable of modulating drug release, enhancing residence time, and improving patient compliance. This review consolidates formulation-oriented knowledge while addressing translational, manufacturing, and regulatory considerations.
KEY FINDINGS
Hydrogels are classified based on source, polymer type, network charge, physical form, and cross-linking methods. Key excipient properties-including swelling, porosity, mechanical strength, biodegradability, and environmental responsiveness-govern performance. Diverse fabrication techniques support tailored design for oral, topical, transdermal, ocular, rectal, and injectable delivery. Challenges such as scalability and reproducibility persist, while stimuli-responsive and composite hydrogels offer promising solutions.
CONCLUSION
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
Nanofiber technology is a revolutionary platform for drug delivery due to its unique physicochemical characteristics, including a high surface‐to‐volume ratio, adjustable porosity, modifiable mechanical strength, and customizable surface chemistry. Combining nanoscale physics and polymer chemistry allows the directed loading, release rates and interaction with biology to be controlled. This review critically examines the underlying physics and chemistry of nanofiber manufacturing and their effects on drug delivery, transport, biological behavior, and clinical translation potential. A literature‐based study was undertaken that was based upon the principles of electrospinning, the chemistry of polymers, incorporation of drugs, kinetics of drug transport, mathematical models, physicochemical characterization, biological interactions and emerging multifunctional nanofiber systems. Diffusion and polymer degradation are the most important mechanisms that determine the release of drugs through nanofibers and are highly dependent on the morphology, porosity, hydrophilicity, and molecular interactions of the nanofibers. The recent developments in stimuli‐responsive and hybrid nanofiber systems also allow the targeted, personalized, and controlled delivery of therapeutics. 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. Nevertheless, even with the issues of scalability and regulation, innovations are increasing at a rate that makes them clinically applicable.
Madhavi Porwal, Phool Chandra, S. Sridhar et al.· Polymers for Advanced Techno...· 0 citations
Conventional oral and injectable drug administration still struggles with unstable plasma levels, weak targeting, and considerable systemic toxicity, problems that become especially acute in chronic disease management. Implantable and wearable biomedical devices offer one path around these limits, yet device-only platforms continue to fall short on drug loading, release control, and protection of fragile therapeutics. Integrating nanoparticle-based biomaterials into such devices has therefore moved from a research curiosity to a serious clinical strategy. As a result, understanding the design principles, translational challenges, and clinical potential of these hybrid platforms has become increasingly important. This review provides a comprehensive assessment of four major nanoparticle families—polymeric carriers (PLGA, chitosan, and micelles), lipid-based vehicles (liposomes, SLNs, and NLCs), inorganic systems (gold, mesoporous silica, iron oxide, and calcium phosphate), and hybrid composites—focusing on how their physicochemical properties govern drug encapsulation, release behavior, and tissue compatibility. These classes are then linked to specific implantable formats such as drug-eluting stents, nano-enabled scaffolds, and reservoir depots, and to wearable formats including transdermal patches, microneedle arrays, biosensor-coupled patches, and patient-actuated devices. A dedicated section addresses stimuli-responsive release driven by pH, enzymes, temperature, and electrical or magnetic fields, alongside closed-loop platforms that pair real-time biosensing with on-demand dosing. Surface engineering strategies, ligand targeting, antifouling coatings, antimicrobial layers, and immune-modulating chemistries are also discussed, together with the central translational hurdles: long-term stability, foreign body response, scale-up, sterilization, and regulatory classification of combination products. Finally, the review outlines near-term directions, including AI-driven dosing, 4D bioprinting, biomimetic nanocarriers, gene therapy delivery, and bioresorbable electronics, that together suggest where these hybrid platforms are likely to mature next.
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