Jul 2026· Naveen International Journal of Multidisciplinary Sciences (NIJMS)· Vol 2, pp. 01-16· 0 citations· 16 references
TL;DR
The study highlights the promising applications of smart polymers in precision medicine, allowing for targeted therapeutic interventions that are more effective and less harmful to the body.
Abstract
Smart polymers, a novel paradigm shift in the pharmaceutical science, are intelligent biomaterials that are designed to react dynamically to external and internal stimuli (e.g., pH, temperature, redox potential, light, and enzyme activities) that allow precise spatiotemporal drug delivery. This thorough study delves into the structure, response mechanisms and pharmaceutical uses of stimuli-responsive polymers for controlled drug delivery. We explore the various facets of smart polymers through the analysis of recent studies, which include pH responsive alginate derivatives with a 43.3% drug release at acidic tumour pH, temperature responsive poly(N-isopropylacrylamide) with tunable LCSTs around the physiological temperature, redox responsive systems with 98.2% cumulative release in reductive environment, and light responsive nanoparticles in which drug release is controlled by light. We investigated both dual and multi-responsive systems, synthesis techniques, in vitro/in vivo efficacy evaluation, and characterization techniques. Results have shown that pH-responsive hydrogels can successfully close wounds in 15 days with closure rate of 90.5%, redox-sensitive polymersomes can be used to successfully encapsulate doxorubicin with high efficiency of 98%, and enzyme-responsive formulations can be used to trigger de-PEGylation mechanisms for effective cellular uptake at high efficiency with pH increase rate in degradation of 2.05-fold per 10°C. The targeting ligands, surface functionalization, and multi-stimuli responsive properties greatly contribute to the improvement of therapeutic specificity and the reduction of off-target toxicity. The study highlights the promising applications of smart polymers in precision medicine, allowing for targeted therapeutic interventions that are more effective and less harmful to the body.
Keywords: stimuli-responsive polymers, pH-responsive systems, redox-triggered delivery, thermosensitive hydrogels, light-responsive nanoparticles, targeted drug delivery.
Stimuli-responsive smart polymers are in a paradigm shift of pharmaceutical delivery systems that can be used to control drug release kinetics in unprecedented detail through external and internal environmental triggers. This study systematically addresses the development, characterization and clinical applications of smart polymer systems for controlled drug delivery. The research goals were to evaluate the effectiveness of pH responsive, temperature responsive, and dual-stimulus polymers in altering drug release patterns, and to correlate the polymer's physicochemical attributes to therapeutic effects. The methodology used was a comprehensive systematic review, which included a review of 87 published studies (2019-2025) from peer-reviewed journals from PubMed and Google Scholar. This hypothesis proposed that polymers with multiple stimulus-responsive properties would exhibit higher bioavailability (>75%) than polymers with a single stimulus-responsive property. The results showed that the pH-responsive poly (methacrylic acid) systems showed drug release efficiency in the range of 68–82% in simulated intestinal fluid and the temperature-responsive poly(N-isopropylacrylamide) systems showed precise release with minimal burst release (<15%) at temperature 37°C. The optimal performance was observed for dual-stimulus systems (pH and temperature responsiveness) and 85-92% cumulative drug release with lower cytotoxicity profiles. The release kinetics of different polymer types were significantly different (p<0.05) based on the statistical analysis. Overall, multi-stimulus responsive polymer systems exhibit a better controlled release profile and thus higher therapeutic potential for the treatment of cancer, diabetes and inflammatory diseases and thus, are promising to be translated into clinical applications.
Keywords: Stimuli-responsive polymers; Controlled drug delivery; Smart polymer systems; pH-responsive hydrogels; Drug release kinetics.
Varleen Kaur, Dr. Ashish Narain Dubey· VED International Journal of...· 0 citations
Stimuli-responsive drug-delivery systems (SRDDS) have transformed precision medicine by enabling spatiotemporal control over therapeutic release, significantly reducing off-target toxicity while enhancing efficacy at the disease site. Naturally occurring polysaccharides, such as hyaluronic acid, chitosan, alginate, and dextran stand out as premier scaffolds for these “smart” nanoplatforms due to their inherent biocompatibility, biodegradability, and abundance of reactive sites for molecular engineering. This review explores the versatility of polysaccharide functionalization, detailing how the introduction of molecular “switches” allows these biopolymers to sense and respond to specific physiological triggers. We analyze the mechanisms behind acid–labile bonds for pH-triggered release, redox-sensitive bridges for intracellular delivery, and enzyme-cleavable sequences for bio-catalytic activation. By bridging the gap between molecular functionalization and clinical utility, these bio-responsive polysaccharide architectures enable integrated physiological monitoring and theranostic applications. This review highlights the impact of these advancements in overcoming biological barriers, providing a sophisticated blueprint for the next generation of nature-derived, “intelligent” biomaterials in cancer therapy.
Stimuli-responsive hydrogels are hydrophilic, three-dimensional polymer network structures that dynamically adjust their properties in response to changes in their external environment, such as temperature, pH, light, electric and magnetic fields, and enzymes. The ease of tuning their physicochemical properties and network architecture gives them an advantage over conventional hydrogels in various applications. This review provides an overview of recent advances in stimuli-responsive hydrogels and critically discusses developments in tissue engineering, food technology, wound healing, controlled drug delivery, and regenerative medicine. Representative examples demonstrate how responsive hydrogel systems can improve cell delivery, tissue regeneration, active food packaging, targeted nutrient release, and infection control. In addition, we also cover a section on the role of neutron scattering techniques, including small-angle neutron scattering (SANS), neutron reflectivity (NR), and quasi-elastic neutron scattering (QENS), in elucidating the network structure of hydrogels, interfacial properties, and molecular dynamics across multiple length and time scales. Finally, 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
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
Sedhu Raagavan Sarkgunan, Benjamin Jeganathan, Rajesh Sathiyamoorthy et al.· Current Pharmaceutical Resea...· 0 citations
Most active pharmaceutical ingredients (APIs) reach their target by passive systemic distribution, so the dose required for efficacy at the lesion is set by what healthy tissue can tolerate; conventional dosage forms consequently produce pharmacokinetic profiles that oscillate between toxic peaks and sub-therapeutic troughs. Nanoparticulate carriers (liposomes, lipid nanoparticles, polymeric and inorganic systems, and biomimetic carriers) and hydrogels (natural, synthetic, supramolecular, and microgel-assembled) have emerged as the dominant strategies to address this, increasingly combined as hybrid nanoparticle–hydrogel constructs in which the gel provides locoregional retention and the nanoparticles provide cargo protection, intracellular delivery and stimuli responsiveness. Stimuli-responsive chemistries (pH, redox, enzyme, ROS, hypoxia, temperature, light, magnetic, ultrasound, glucose, and multi-stimuli logic) translate the molecular signatures of a disease into spatiotemporally controlled cargo release. This narrative review consolidates the state of the art (prioritizing 2022–2026) and departs from the conventional carrier-type survey in one respect: the literature is read along an explicit chain—disease cue, sensing chemistry, carrier architecture, release mechanism and kinetics, administration route, and clinical readiness—which exposes a variable that classification by carrier type conceals. Across all three material classes, what governs release behavior is not primarily the carrier chemistry but the identity of the released species (dissolved drug, drug from an embedded nanoparticle, an intact nanoparticle, and a matrix fragment) and the transport step that limits it. This is why power-law exponent analysis developed for dissolved drug fits particulate release poorly, why statistical goodness-of-fit cannot by itself establish a release mechanism, and why carrier class predicts clinical readiness less well than administration route and regulatory product type. Translational hurdles—CMC complexity, regulatory fragmentation, anti-PEG immunogenicity, and the structural mismatch between preclinical promise and clinical efficacy—are critically appraised in light of previously reported <1% delivery efficiency analysis. This review identifies converging strategies that could move stimuli-responsive controlled release from an aspirational outcome to a routine clinical reality.
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