Jul 2026· Biochemical and Biophysical Research Communications - BBRC· Vol 831, pp.
154346
· 0 citations· 82 references
Medicine
TL;DR
This review highlights a formulation-driven framework for the rational design and clinical translation of hydrogel-based pharmaceutical excipients in advanced drug delivery systems.
Abstract
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.
INTRODUCTION
Polysaccharide hydrogels have gained increasing attention as innovative platforms for controlled and stimuli-responsive drug delivery. Inherent biocompatibility, biodegradability and chemical versatility of these materials render them particularly well-suited for biomedical applications. Moreover, their ability to be engineered into 'smart' systems facilitates controlled release of therapeutic agents at target sites. This review summarizes recent advances in synthesis strategies and functional properties of polysaccharide hydrogels relevant for drug delivery.
AREAS COVERED
Mechanical tunability, responsiveness to physiological stimuli and affinity-based interactions are analyzed with regards to their impact on therapeutic efficacy. Key hurdles such as manufacturing scalability, reproducibility, regulatory compliance, challenge of balancing biodegradability with mechanical stability and controlled drug release are critically discussed. Proof-of-concept studies are highlighted spanning preclinical in vivo models, as well as early clinical trials exploring application in oncology, regenerative medicine and pain management.
EXPERT OPINION
Polysaccharide-based stimuli-responsive and multifunctional hydrogels represent highly promising platforms for controlled and targeted drug delivery. While recent advances in biofabrication and nanotechnology have significantly expanded their therapeutic potential, important challenges including scalability, reproducibility, and clinical translation, still need to be addressed. In particular, limited availability of long-term in vivo safety and efficacy data remains a major barrier to broader clinical application.
Gioconda Millotti, Flavia Laffleur, Agnes Kestler· Expert Opinion on Drug Deliv...· 0 citations
Oral drug delivery is preferred for patient compliance, but it's challenging for biologics and sensitive therapeutics due to the harsh gastrointestinal environment. Engineered oral hydrogels, enhanced through chemical modifications, offer superior entrapment efficiency and controlled release compared to traditional forms like capsules. Through innovative mechanisms, including stimuli-responsiveness, active adhesion, and microenvironmental modulation, oral hydrogels overcome key limitations associated with traditional oral formulations. These systems can achieve prolonged retention and site-specific controlled release in targeted areas of the gut, such as the colon, through chemical engineering strategies. Meanwhile, they can also be used as bioactive ingredients to regulate intestinal microbiota, restore the integrity of the mucosal barrier, and play a systemic therapeutic role in distal organs through the gut-brain axis and gut-immune axis. This review summarizes the research progress of oral hydrogel materials, focusing on their stimuli-responsive and mucus-adhesive designs for efficient drug delivery, as well as extended functions such as regulation of intestinal microbiota. It also addresses the challenges of clinical translation and examines bottlenecks and regulatory pathways to scale up through disease-specific cases. Finally, an integrated framework combining rational design, artificial intelligence, and translational science is proposed to bridge the gap from laboratory research to clinical applications.
Dongyan Liu, Bei Guo, Fei Qin et al.· Journal of Controlled Releas...· 0 citations
Conventional hydrogel systems for biomedical applications face critical limitations in mechanical robustness, therapeutic functionality, and responsiveness to physiological stimuli, hindering their translation to precision medicine. The rational integration of engineered nanomaterials into injectable hydrogel matrices has emerged as a transformative strategy to overcome these constraints, enabling hierarchical, stimuli-responsive functionalities unattainable in traditional polymer networks. This review provides a mechanistic and translational analysis of injectable nanocomposite (NC) hydrogels, systematically examining how nanoparticle-polymer interfacial interactions govern gelation kinetics, mechanical properties, and controlled therapeutic release. Unlike previous reviews focused on material cataloguing, we critically evaluate the distinctive advantages of NC hydrogels over conventional dynamic hydrogels; including hierarchical drug release profiles, enhanced tumour penetration, and multiscale environmental responsiveness; whilst providing evidence-based assessment of clinical translation pathways. The strategic incorporation of metal-based nanostructures, carbon nanomaterials, lipid carriers, and black phosphorus nanosheets is analysed across four key biomedical domains: advanced drug delivery systems, tissue engineering scaffolds, chronic wound healing platforms, and biosensing technologies. We provide systematic coverage of injectability parameters, smart responsive behaviours, and patient-specific customisation strategies essential for minimally invasive delivery. Critically, this review addresses the gap between preclinical promise and clinical reality by examining actual clinical trial data, regulatory challenges, and manufacturing scalability barriers. Emerging artificial intelligence and machine learning tools for accelerated NC hydrogel design, predictive modelling, and real-time therapeutic monitoring are evaluated as enabling technologies for next-generation precision biomedicine. This comprehensive roadmap equips researchers and clinicians with mechanistic frameworks and practical guidance for translating injectable NC hydrogels from laboratory innovation to clinical impact.
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 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.