Aug 2026· Current Pharmaceutical Research· 0 citations· 75 references
TL;DR
This review aims to provide a comprehensive summary of the current advances, mechanisms, and perspectives of smart stimuli-responsive injectable hydrogels, including their successful outcomes in completely curing tumours, 75% tumour regression using a GSH-responsive peptide gel, and significant functional repair in spinal cord injury repairs using microenvironment-responsive matrices.
Abstract
Smart stimuli-responsive injectable hydrogels are new generation of drug delivery systems that promise to revolutionize the field of drug delivery by combining the benefits of minimally invasive drug delivery systems with spatial and temporal control over drug release. This report aims to summarize the recent advances in the design of stimuli-responsive injectable hydrogels, including the polymer backbone, such as polysaccharide-derived hyaluronic acid, and synthetic poly(NIPAM), poly(PEG), and poly(zwitterionic)s, as well as the various cross-linking chemistries, including Schiff base, Michael addition, and physical cross-linking, that enable the design of injectable hydrogels that undergo a solution-to-gel transition in situ in response to various stimuli, such as pH, redox, enzymes, light, ultrasound, and temperature, among others. This review aims to provide a comprehensive summary of the current advances, mechanisms, and perspectives of smart stimuli-responsive injectable hydrogels, including their applications in oncology, ophthalmology, and neurology, as well as their successful outcomes in completely curing tumours, 75% tumour regression using a GSH-responsive peptide gel, and significant functional repair in spinal cord injury repairs using microenvironment-responsive matrices, among many other applications of injectable hydrogels in drug delivery systems. The translation of injectable hydrogels into the clinic, however, is currently hampered by the difficulties in long-term biocompatibility profiling, large-scale sterile production, and regulatory hurdles associated with combination drug products
Stimulus-responsive cellulose-based hydrogels combine the advantages of being widely sourced, renewable, biocompatible, and biodegradable. With their three-dimensional porous networks and high water content, they provide an ideal environment for drug loading, diffusion, and cell growth. Through chemical modification, physical crosslinking, chemical crosslinking, or composite network design, cellulose-based hydrogels can respond to pH, temperature, light, and multi-stimuli, and achieve controlled drug release by adjusting network pore size, swelling behavior, crosslinking density, or degradation rate. This review summarizes the structural characteristics of cellulose and its derivatives, the main preparation methods of cellulose-based hydrogels, their stimulus-responsive mechanisms, and recent advances in their application for drug delivery. It focuses on their potential applications in anticancer drug delivery, wound dressings and antimicrobial delivery, ophthalmic drug delivery, oral-intestinal drug delivery, as well as tissue engineering and regenerative medicine. Finally, this paper summarizes the challenges facing these materials in terms of mechanical properties, release behavior stability, in vivo compatibility, and large-scale application, and outlines future directions for their development.
Wenyu Luo· Theoretical and Natural Scie...· 0 citations
An overview of recent advances in stimuli-responsive hydrogels is provided and current challenges related to scalability, biocompatibility, regulatory approval, and commercialization are discussed, along with future perspectives on translating smart and self-healing hydrogel technologies into practical applications in food, biomedical, and tissue engineering.
Brijitta Joseph, A. Bharati, D. Saha· Frontiers in Soft Matter· 0 citations
This narrative review consolidates the state of the art and departs from the conventional carrier-type survey and identifies converging strategies that could move stimuli-responsive controlled release from an aspirational outcome to a routine clinical reality.
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
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
Hydrogels are three-dimensional hydrophilic polymeric networks known for their high water absorption capacity, biocompatibility, biodegradability, and resemblance to the natural extracellular matrix, making them highly valuable in pharmaceutical and biomedical applications. Recent advances in polymer science, nanotechnology, and bioengineering have led to the development of smart, injectable, self-healing, and nanocomposite hydrogels with improved mechanical strength and stimuli-responsive behavior. These advanced hydrogel systems have shown significant potential in controlled drug delivery, wound healing, tissue engineering, regenerative medicine, cancer therapy, and ophthalmic applications. Emerging fabrication technologies such as 3D/4D bioprinting, microfluidics, and electrospinning have further enhanced the design and functionality of hydrogel-based systems. Despite promising progress, challenges related to scalability, long-term stability, sterilization, and clinical translation still remain. This review highlights recent advances in hydrogel synthesis, characterization, biomedical applications, clinical developments, and future perspectives, emphasizing the growing importance of hydrogels as next-generation biomaterials in modern healthcare.
Sachin, Virendra kumar Maurya, Kamalesh Kumar· GLOBAL JOURNAL OF PHARMACEUT...· 0 citations
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