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The emergence of stimuli-responsive drug delivery systems (SRDDS), often referred to as smart drug delivery platforms, represents a transformative leap in the field of pharmaceutical technology. By harnessing specific internal or external stimuli, these innovative systems offer the capability to release therapeutic agents in a controlled manner with high precision, targeting specific tissues or pathological sites. This targeted delivery approach not only maximizes drug efficacy but also substantially reduces adverse effects commonly associated with conventional therapies. In this comprehensive review, we explore the diverse categories of stimuli that can trigger drug release, including but not limited to pH variations, temperature changes, enzymatic activity, redox conditions, light, magnetic fields, and ultrasound. The discussion extends to the design principles underlying the construction of smart materials and Nano carriers capable of responding to these cues, emphasizing polymeric structures, lipid-based systems, inorganic nanoparticles, and hybrid assemblies. Detailed examination of drug release mechanisms reveals how these systems translate environmental changes into physicochemical responses that facilitate precise drug liberation. Additionally, the review highlights significant biomedical applications of SRDDS across various disease models, including cancer, neurological disorders, inflammation, and infectious diseases. Attention is also given to the recent advances in multifunctional platforms that combine diagnostic and therapeutic functions, often referred to as theranostics. Despite promising developments, several challenges remain, such as reproducibility, scalability, biocompatibility, regulatory approval, and clinical translation. This article concludes by outlining future directions, focusing on the integration of personalized medicine, advanced biomaterials, and smart manufacturing technologies to further refine and optimize SRDDS for widespread clinical use.
Keywords
pH-sensitive delivery, Temperature-responsive systems, Enzyme-triggered drug release
Introduction
Traditional drug delivery methods are limited by systemic distribution, poor solubility, and uncontrolled release rates, often leading to suboptimal therapeutic outcomes and adverse side effects. Stimuli-responsive drug delivery systems have emerged to address these challenges by releasing drugs selectively in response to specific environmental cues, thereby increasing drug accumulation at target sites and improving pharmacokinetics. SRDDS harness the unique physiological and pathological differences between healthy and diseased tissues—such as acidic pH, elevated enzyme levels, or redox potential—to trigger drug release. Additionally, externally applied stimuli like heat, light, or magnetic fields can be used to remotely control drug release. These systems integrate advances in nanotechnology, polymer chemistry, and molecular biology, making them promising candidates for precision medicine.
2. Classification Of Stimuli-Responsive Systems
Stimuli-responsive drug delivery systems (SRDDS) are broadly categorized based on the type of stimulus they respond to — either endogenous (originating inside the body) or exogenous (applied from outside the body).
2.1 Endogenous Stimuli-Responsive Systems
These systems use internal physiological or pathological differences between healthy and diseased tissues to trigger drug release specifically at the disease site.
2.1.1 pH-Responsive Systems
Many pathological environments, such as tumors or inflamed tissues, have an acidic pH (around 5.0 to 6.8), compared to the normal physiological pH of ~7.4 found in healthy tissues and blood. Drug carriers can be engineered to exploit this acidity by incorporating pH-sensitive components:
Design Strategies: Acid-labile chemical bonds (like hydrazone, imine, cis-aconityl) are included in the drug-carrier complex. These bonds remain stable at physiological pH but break under acidic conditions, releasing the drug.
Materials: Polymers like poly(β-amino ester), poly(L-histidine), and polyketal are commonly used because they either degrade, swell, or change solubility in response to lower pH, facilitating targeted drug release specifically at diseased sites.
2.1.2 Enzyme-Responsive Systems
Certain enzymes are overexpressed in disease environments (e.g., cancer or arthritic tissue), providing a trigger for site-specific drug release:
Example Enzymes: Matrix metalloproteinases (MMPs) are enzymes elevated in tumor microenvironments.
Mechanism: Drug carriers contain peptide linkers or coatings that are specifically cleaved by these enzymes. Once the carrier encounters these enzymes, the peptide bonds are cleaved, causing carrier breakdown and targeted drug release.
Example: Nanoparticles coated with peptides sensitive to MMP-2 or MMP-9 degrade in tumor tissues rich in these enzymes, releasing the encapsulated drugs locally.
2.1.3 Redox-Responsive Systems
The intracellular environment of certain diseased cells (notably cancer cells) has higher concentrations of reducing agents such as glutathione (GSH) compared to extracellular fluids.
Mechanism: Drug carriers include disulfide or diselenide bonds that remain intact in oxidizing extracellular conditions but are cleaved in the reducing intracellular environment.
Application: When these bonds are broken inside the cell, the drug is released directly into the cytosol, which is crucial for chemotherapeutic agents that must act intracellularly.
2.2 Exogenous Stimuli-Responsive Systems
These systems respond to stimuli applied from outside the body, allowing external control over drug release timing and location.
2.2.1 Temperature-Responsive Systems
Certain polymers show a sharp change in properties at a specific temperature called the lower critical solution temperature (LCST):
Example Polymer: Poly(N-isopropylacrylamide) (PNIPAAm) swells and is hydrophilic below its LCST (~32°C), but collapses and becomes hydrophobic above it.
Use: Mild heating (40–45°C) from external sources can cause the polymer to collapse and expel the drug. This strategy is especially useful in targeted hyperthermia combined with chemotherapy, allowing localized drug release with minimal side effects.
2.2.2 Light-Responsive Systems
Light can be used for precise spatial and temporal control of drug release:
Mechanisms: Light induces photochemical cleavage of bonds, photoisomerization (changing molecular shape), or photothermal effects (heat generation).
Examples: Drug carriers with photo-cleavable linkers like o-nitrobenzyl release drugs upon light exposure, and gold nanoparticles convert light into heat to trigger drug release through thermal effects.
2.2.3 Magnetic-Responsive Systems
Magnetic nanoparticles can be manipulated externally for targeted drug delivery:
Targeting: An external magnetic field guides magnetic nanoparticles to specific body sites.
Triggering: Applying alternating magnetic fields generates localized heat (magnetic hyperthermia), triggering drug release from heat-sensitive carriers.
Advantages: This is a non-invasive way to control drug release and target deep tissues that are difficult to reach otherwise.
2.2.4 Ultrasound-Responsive Systems
Ultrasound waves cause mechanical effects like cavitation (bubble formation and collapse), which can disrupt drug carriers or increase tissue permeability:
Effect: The mechanical forces break the carrier or open tissue barriers, releasing the drug at the desired site.
Application: Focused ultrasound targets drug release precisely in specific tissues, useful in cancer therapy or localized inflammation.
3. Materials And Design Strategies
3.1 Polymers
Polymers form the backbone of many SRDDS because of their tunable properties:
Biodegradable and biocompatible: Ensures safety and avoids long-term accumulation in the body.
Natural Polymers: Chitosan and hyaluronic acid can be chemically modified to respond to stimuli.
Synthetic Polymers: Examples include PLGA (poly(lactic-co-glycolic acid)), PEG (polyethylene glycol), and PNIPAAm.
Functionalization: pH-sensitive polymers like poly(histidine) and polymethacrylates have acid-labile bonds; redox-sensitive systems use disulfide bonds in the polymer chain or crosslinks.
3.2 Lipid-Based Carriers
Liposomes and solid lipid nanoparticles are lipid-based systems:
Modification: Coating or incorporation of stimuli-sensitive lipids enables triggered drug release.
Advantages: Can encapsulate hydrophilic and hydrophobic drugs and are biocompatible.
3.3 Inorganic Nanoparticles
Examples include mesoporous silica, gold, and iron oxide nanoparticles:
Properties: Easy surface modification and inherent properties (magnetic or photothermal) make them ideal for stimuli-responsive delivery.
Multifunctionality: Can combine drug delivery with imaging or photothermal therapy.
3.4 Hydrogels
Three-dimensional polymer networks that swell or shrink in response to stimuli:
Function: Regulate drug release by changing mesh size.
Applications: Localized drug delivery and tissue engineering scaffolds.
4. Mechanisms Of Drug Release (Detailed)
The way drugs are released from stimuli-responsive carriers depends on how the carrier interacts with the trigger (stimulus). These mechanisms are crucial because they determine how precisely and efficiently a drug can be delivered to its target site.
4.1 Swelling and Deswelling
Swelling: When exposed to a specific stimulus (e.g., pH, temperature), the polymer matrix absorbs water and swells, increasing the size of the pores or mesh network within the carrier. This expansion allows encapsulated drug molecules to diffuse out more easily into the surrounding environment.
Deswelling: Conversely, some stimuli cause the polymer to shrink or collapse, actively squeezing out the drug molecules. For example, temperature-responsive polymers like PNIPAAm collapse above their LCST, pushing the drug out.
Impact: This mechanism enables a controlled, gradual release that can be tuned by altering the polymer composition or crosslink density.
4.2 Bond Cleavage and Degradation
Chemical Bond Cleavage: Stimuli like acidic pH, enzymes, or redox agents break specific chemical bonds within the carrier matrix or between the drug and carrier. For instance, acid-labile hydrazone bonds in pH-responsive systems cleave in acidic environments, releasing the drug.
Polymer Degradation: The carrier polymer itself may degrade under stimuli, releasing the drug. Enzyme-sensitive polymers are broken down by overexpressed enzymes at disease sites, while redox-sensitive polymers degrade in the reducing intracellular environment.
Outcome: This mechanism results in a triggered burst or sustained release depending on the rate of bond cleavage and degradation.
4.3 Structural Reconfiguration
Stimuli can induce changes in the physical structure of the carrier, such as micelle disassembly, vesicle rupture, or polymer conformational changes.
For example, enzyme cleavage may destabilize nanoparticle coatings, causing the carrier to disassemble and release the drug payload.
These changes often lead to a rapid release of the drug, useful for on-demand therapy.
4.4 Phase Transition
Polymers like PNIPAAm exhibit reversible phase transitions near body temperature.
Below the LCST, the polymer is hydrophilic and swollen; above it, it becomes hydrophobic and collapses.
This reversible transition can be harnessed to trigger drug release by applying mild heating (e.g., in hyperthermia therapy), causing the polymer to expel the drug as it collapses.
5. Applications
5.1 Cancer Therapy
Tumor microenvironments exhibit unique features such as acidic pH, high glutathione levels, and elevated enzymes like MMPs.
SRDDS can be engineered to release chemotherapeutic drugs selectively at tumors, minimizing damage to healthy tissue.
Examples include pH-sensitive nanoparticles that release drugs in acidic tumor tissue or redox-responsive carriers that release drugs inside cancer cells.
This targeted approach reduces systemic toxicity and improves treatment efficacy.
5.2 Treatment of Inflammatory Diseases
Inflammation sites have altered pH, elevated enzymes (e.g., phospholipases), and oxidative stress.
Stimuli-responsive systems can deliver anti-inflammatory drugs specifically to these regions.
Controlled drug release at inflammation sites reduces side effects and improves patient outcomes in diseases like rheumatoid arthritis or inflammatory bowel disease.
5.3 Gene and Protein Delivery
Biological therapeutics like DNA, RNA, and proteins are fragile and degrade quickly in the body.
SRDDS protect these molecules during circulation and enable controlled release inside target cells.
For example, redox-sensitive carriers release gene therapies in the cytosol, where reducing conditions prevail.
This targeted intracellular delivery is essential for effective gene editing or protein replacement therapies.
5.4 Diagnostic and Theranostic Applications
Theranostics combines therapy and diagnostics into one platform.
Stimuli-responsive carriers can be loaded with imaging agents (e.g., MRI contrast agents, fluorescent dyes) alongside drugs.
This allows simultaneous monitoring of drug delivery, biodistribution, and therapeutic efficacy in real time.
Examples include gold nanoparticles that serve as photothermal therapy agents and imaging contrast simultaneously
6. Recent Innovations
6.1 Multi-Stimuli Responsive Systems
Combining multiple stimuli responses (e.g., pH + redox, or temperature + magnetic field) increases targeting accuracy.
Multi-responsive carriers can overcome the limitations of single stimuli, reducing premature drug release and enhancing control.
Example: A nanoparticle that remains stable in the bloodstream but releases its cargo only in acidic, enzyme-rich tumor environments exposed to mild heat.
6.2 Personalized Medicine
Advances in biomarker detection allow the design of SRDDS tailored to an individual’s disease profile.
Patient-specific triggers (such as enzyme expression levels or unique microenvironment conditions) can be used to optimize drug release profiles.
This personalization improves treatment outcomes and minimizes adverse effects.
6.3 Biodegradable and Sustainable Systems
There is increasing focus on designing fully biodegradable carriers that leave no harmful residues.
Sustainable materials sourced from natural polymers or green chemistry approaches reduce environmental impact.
Biodegradable systems also improve safety by preventing long-term accumulation in the body.
7. Challenges
7.1 Biological Barriers
Immune Clearance: Nanocarriers are often recognized and eliminated by the immune system (e.g., via macrophages), reducing their circulation time and efficacy.
Opsonization: Serum proteins bind to nanoparticles, marking them for clearance.
Poor Tissue Penetration: Dense extracellular matrices, high interstitial pressure, and abnormal vasculature in tumors can limit carrier penetration.
Strategies like PEGylation (adding PEG chains) and size optimization help but are not always fully effective.
7.2 Safety and Toxicity
Long-term safety of novel materials and their degradation products must be established.
Some carriers may accumulate in organs like the liver or spleen, causing toxicity.
Thorough in vitro and in vivo studies are required to evaluate immune reactions, inflammation, and genotoxicity.
7.3 Manufacturing and Scalability
Producing SRDDS with consistent size, drug loading, and stimuli responsiveness at industrial scale is difficult.
Complex synthesis and purification steps increase costs.
Batch-to-batch variability can impact clinical efficacy.
Scaling up requires standardization of protocols and quality control.
7.4 Regulatory Approval
Lack of standardized regulatory guidelines for evaluating complex stimuli-responsive systems delays approval.
Regulatory agencies require extensive data on safety, efficacy, and manufacturing processes.
Multi-component systems with novel materials face additional hurdles.
8. CONCLUSION
To sum up, stimuli-responsive drug delivery systems have introduced a new paradigm in targeted therapy by enabling precise control over drug release in response to specific biological or external cues. These systems improve the efficiency of treatments by concentrating therapeutic agents at disease sites while minimizing systemic exposure and side effects. Innovations in material design have produced sophisticated carriers capable of reacting to multiple stimuli, enhancing their versatility and functionality. Nevertheless, translating these promising technologies from laboratory research to clinical use still faces hurdles, including manufacturing challenges, safety concerns, and regulatory complexities. Addressing these issues through continued research and collaboration across disciplines will be crucial for the successful integration of smart delivery systems into mainstream medical practice. With ongoing advancements, stimuli-responsive platforms hold significant promise for revolutionizing personalized medicine and improving patient outcomes in the years ahead.
REFERENCES
Wang S. "A comprehensive review of conventional and stimuli-responsive delivery systems designed to enhance stability and bioavailability." Emergent Materials, 2025.
Dai XJ, Li WJ, Xie DD. "Stimuli-Responsive Nano Drug Delivery Systems for the Treatment of Neurological Diseases." Small, 2025.
Zhou L, et al. "Stimuli-responsive peptide-based nanodrug delivery systems for tumor therapy." Chemical Communications, 2025.
Gade L. "Stimuli-responsive drug delivery systems for inflammatory skin disease." Advanced Drug Delivery Reviews, 2024.
Singh D, et al. "Stimuli responsiveness of recent biomacromolecular drug delivery systems." International Journal of Biological Macromolecules, 2024.
Xu H, et al. "Recent advances in multi-stimuli-responsive polymeric nanocarriers for cancer therapy." Biomaterials Science, 2025.
Patel R, et al. "Enzyme-responsive nanocarriers in targeted cancer drug delivery." Pharmaceutical Research, 2024.
Banerjee S, et al. "Redox-responsive smart drug delivery platforms: design, challenges, and biomedical relevance." ACS Applied Nano Materials, 2024.
Lee H, et al. "Temperature-sensitive hydrogels for controlled release in wound healing." Journal of Biomedical Materials Research, 2025.
Kim SH, et al. "NIR-light triggered release in gold nanoparticle-based nanomedicines." Theranostics, 2024.
Sharma P, et al. "Magnetic nanoparticle-based stimulus-responsive drug delivery for deep tissue targeting." Frontiers in Nanomedicine, 2025.
Jones MB, et al. "Ultrasound-induced site-specific drug release in polymer nanocapsules." Bioengineering & Translational Medicine, 2025.
Zhang Y, et al. "Multi-stimuli nanocarriers for personalized oncology." Cancer Nanotechnology, 2024.
Qiu L, et al. "Biodegradable polymers for sustainable stimuli-responsive drug delivery." Journal of Polymer Science, 2024.
Alsaab HO, et al. "PEGylated nanoformulations for evading immune clearance." Drug Delivery and Translational Research, 2025.
Moradi S, et al. "Hydrazone bond-based systems for pH-responsive drug release." Pharmaceutics, 2024.
Rao SS, et al. "Solid lipid nanoparticles in stimuli-responsive anticancer delivery." Nanomedicine, 2024.
Tang J, et al. "Polyketal-based smart carriers for inflammation therapy." Advanced Healthcare Materials, 2025.
Li N, et al. "Matrix metalloproteinase-sensitive nanostructures for targeted chemotherapy." Expert Opinion on Drug Delivery, 2025.
Singh J, et al. "Chitosan modified hydrogels for dual-stimulus drug delivery." Carbohydrate Polymers, 2024.
Nguyen PM, et al. "Gene delivery via redox-responsive polymeric vesicles." Biomaterials Research, 2025.
Wei W, et al. "Photothermal liposome systems for simultaneous imaging and drug release." Journal of Controlled Release, 2024.
Lin Y, et al. "Theranostic gold nanocomposites for cancer therapy." Journal of Nanobiotechnology, 2025.
Park SY, et al. "Multi-responsive dendrimeric nanocarriers." Molecular Pharmaceutics, 2024.
Hassan A, et al. "Safety and toxicity assessment of nanomaterial-based SRDDS." Toxicology Letters, 2024.
Martínez Á, et al. "Challenges in SRDDS manufacturing and scalability." Drug Design, Development and Therapy, 2025.
Ramasamy T, et al. "Regulatory advances and hurdles for smart drug delivery." Pharmaceutical Regulatory Affairs Journal, 2025.
Khanna V, et al. "Sustainable natural polymers in smart DDS design." Materials Today Bio, 2024.
Yadav S, et al. "Targeted therapy for rheumatoid arthritis using enzyme-responsive systems." Journal of Immunology Research, 2025.
Johnson MR, et al. "Hydrogel mesh-size control for variable drug release." Polymers for Advanced Technologies, 2024.
Ye Z, et al. "Opsonization minimization using surface engineering in DDS." Trends in Biotechnology, 2024.
Chen X, et al. "Solid-phase synthesis for scalable SRDDS carriers." Biochemical Engineering Journal, 2025.
Gupta AK, et al. "Phase transition-based PNIPAAm hydrogels in localized cancer therapy." International Journal of Pharmaceutics, 2024.
Fernandes C, et al. "Stimuli-responsive nanoemulsions in protein delivery." Nanomedicine: NBM, 2025.
Garcia M, et al. "Biocompatibility studies of nanocarrier degradation products." Journal of Biomedical Nanotechnology, 2024.
Mehta V, et al. "Poly(β-amino ester) in gene therapy." Molecular Therapy Nucleic Acids, 2024.
Silva P, et al. "Hybrid nanocarriers for dual photothermal/chemotherapy." Advanced Drug Delivery Reviews, 2025.
Lu Z, et al. "Patient-specific biomarkers for personalized SRDDS." Personalized Medicine, 2024.
Yang S, et al. "pH and enzyme dual-responsive microgels for anti-inflammatory therapy." Colloids and Surfaces B: Biointerfaces, 2025.
Onwudiwe G, et al. "Micelle disassembly-triggered release in stimuli-responsive DDS." Soft Matter, 2025.
Jiang Y, et al. "Redox-sensitive vesicles for intracellular delivery." Bioengineering, 2024.
Kelkar SS, et al. "PEGylation and immune modulation in nanodrug delivery." Journal of Biomaterials Applications, 2025.
Rodriguez S, et al. "Clinical translation prospects for multi-stimuli therapies." Translational Medicine Communications, 2024.
Maiti S, et al. "Design of hydrogels for site-specific protein delivery." Acta Biomaterialia, 2025.
Dutta SK, et al. "Iron oxide magnetic carriers for deep tissue cancer targeting." Journal of Controlled Release, 2024.
Lim JA, et al. "Light-responsive carriers for chronotherapy in oncology." Pharmaceuticals, 2024.
Ozturk S, et al. "Dendrimer nanoparticles in gene and protein delivery." Expert Opinion on Drug Delivery, 2025.
Gomez L, et al. "Smart liposomes in diagnostic imaging and drug release." Future Science OA, 2024.
Patel Y, et al. "Batch-to-batch consistency in SRDDS synthesis." Process Biochemistry, 2025.
Kumari S, et al. "Current advances in green chemistry for SRDDS fabrication." Green Chemistry, 2024.
Reference
Wang S. "A comprehensive review of conventional and stimuli-responsive delivery systems designed to enhance stability and bioavailability." Emergent Materials, 2025.
Dai XJ, Li WJ, Xie DD. "Stimuli-Responsive Nano Drug Delivery Systems for the Treatment of Neurological Diseases." Small, 2025.
Zhou L, et al. "Stimuli-responsive peptide-based nanodrug delivery systems for tumor therapy." Chemical Communications, 2025.
Gade L. "Stimuli-responsive drug delivery systems for inflammatory skin disease." Advanced Drug Delivery Reviews, 2024.
Singh D, et al. "Stimuli responsiveness of recent biomacromolecular drug delivery systems." International Journal of Biological Macromolecules, 2024.
Xu H, et al. "Recent advances in multi-stimuli-responsive polymeric nanocarriers for cancer therapy." Biomaterials Science, 2025.
Patel R, et al. "Enzyme-responsive nanocarriers in targeted cancer drug delivery." Pharmaceutical Research, 2024.
Banerjee S, et al. "Redox-responsive smart drug delivery platforms: design, challenges, and biomedical relevance." ACS Applied Nano Materials, 2024.
Lee H, et al. "Temperature-sensitive hydrogels for controlled release in wound healing." Journal of Biomedical Materials Research, 2025.
Kim SH, et al. "NIR-light triggered release in gold nanoparticle-based nanomedicines." Theranostics, 2024.
Sharma P, et al. "Magnetic nanoparticle-based stimulus-responsive drug delivery for deep tissue targeting." Frontiers in Nanomedicine, 2025.
Jones MB, et al. "Ultrasound-induced site-specific drug release in polymer nanocapsules." Bioengineering & Translational Medicine, 2025.
Zhang Y, et al. "Multi-stimuli nanocarriers for personalized oncology." Cancer Nanotechnology, 2024.
Qiu L, et al. "Biodegradable polymers for sustainable stimuli-responsive drug delivery." Journal of Polymer Science, 2024.
Alsaab HO, et al. "PEGylated nanoformulations for evading immune clearance." Drug Delivery and Translational Research, 2025.
Moradi S, et al. "Hydrazone bond-based systems for pH-responsive drug release." Pharmaceutics, 2024.
Rao SS, et al. "Solid lipid nanoparticles in stimuli-responsive anticancer delivery." Nanomedicine, 2024.
Tang J, et al. "Polyketal-based smart carriers for inflammation therapy." Advanced Healthcare Materials, 2025.
Li N, et al. "Matrix metalloproteinase-sensitive nanostructures for targeted chemotherapy." Expert Opinion on Drug Delivery, 2025.
Singh J, et al. "Chitosan modified hydrogels for dual-stimulus drug delivery." Carbohydrate Polymers, 2024.
Nguyen PM, et al. "Gene delivery via redox-responsive polymeric vesicles." Biomaterials Research, 2025.
Wei W, et al. "Photothermal liposome systems for simultaneous imaging and drug release." Journal of Controlled Release, 2024.
Lin Y, et al. "Theranostic gold nanocomposites for cancer therapy." Journal of Nanobiotechnology, 2025.
Park SY, et al. "Multi-responsive dendrimeric nanocarriers." Molecular Pharmaceutics, 2024.
Hassan A, et al. "Safety and toxicity assessment of nanomaterial-based SRDDS." Toxicology Letters, 2024.
Martínez Á, et al. "Challenges in SRDDS manufacturing and scalability." Drug Design, Development and Therapy, 2025.
Ramasamy T, et al. "Regulatory advances and hurdles for smart drug delivery." Pharmaceutical Regulatory Affairs Journal, 2025.
Khanna V, et al. "Sustainable natural polymers in smart DDS design." Materials Today Bio, 2024.
Yadav S, et al. "Targeted therapy for rheumatoid arthritis using enzyme-responsive systems." Journal of Immunology Research, 2025.
Johnson MR, et al. "Hydrogel mesh-size control for variable drug release." Polymers for Advanced Technologies, 2024.
Ye Z, et al. "Opsonization minimization using surface engineering in DDS." Trends in Biotechnology, 2024.
Chen X, et al. "Solid-phase synthesis for scalable SRDDS carriers." Biochemical Engineering Journal, 2025.
Gupta AK, et al. "Phase transition-based PNIPAAm hydrogels in localized cancer therapy." International Journal of Pharmaceutics, 2024.
Fernandes C, et al. "Stimuli-responsive nanoemulsions in protein delivery." Nanomedicine: NBM, 2025.
Garcia M, et al. "Biocompatibility studies of nanocarrier degradation products." Journal of Biomedical Nanotechnology, 2024.
Mehta V, et al. "Poly(β-amino ester) in gene therapy." Molecular Therapy Nucleic Acids, 2024.
Silva P, et al. "Hybrid nanocarriers for dual photothermal/chemotherapy." Advanced Drug Delivery Reviews, 2025.
Lu Z, et al. "Patient-specific biomarkers for personalized SRDDS." Personalized Medicine, 2024.
Yang S, et al. "pH and enzyme dual-responsive microgels for anti-inflammatory therapy." Colloids and Surfaces B: Biointerfaces, 2025.
Onwudiwe G, et al. "Micelle disassembly-triggered release in stimuli-responsive DDS." Soft Matter, 2025.
Jiang Y, et al. "Redox-sensitive vesicles for intracellular delivery." Bioengineering, 2024.
Kelkar SS, et al. "PEGylation and immune modulation in nanodrug delivery." Journal of Biomaterials Applications, 2025.
Rodriguez S, et al. "Clinical translation prospects for multi-stimuli therapies." Translational Medicine Communications, 2024.
Maiti S, et al. "Design of hydrogels for site-specific protein delivery." Acta Biomaterialia, 2025.
Dutta SK, et al. "Iron oxide magnetic carriers for deep tissue cancer targeting." Journal of Controlled Release, 2024.
Lim JA, et al. "Light-responsive carriers for chronotherapy in oncology." Pharmaceuticals, 2024.
Ozturk S, et al. "Dendrimer nanoparticles in gene and protein delivery." Expert Opinion on Drug Delivery, 2025.
Gomez L, et al. "Smart liposomes in diagnostic imaging and drug release." Future Science OA, 2024.
Patel Y, et al. "Batch-to-batch consistency in SRDDS synthesis." Process Biochemistry, 2025.
Kumari S, et al. "Current advances in green chemistry for SRDDS fabrication." Green Chemistry, 2024.
Rushikesh Kumbhar
Corresponding author
D. Y. Patil college of Pharmacy, D. Y. Patil Education Society, Kolhapur.
D. Y. Patil college of Pharmacy, D. Y. Patil Education Society, Kolhapur.
Rushikesh Kumbhar*, Dr. Chandraprabhu Jangme, Stimuli-Responsive (Smart) Drug Delivery Systems: An In-Depth Review, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 8, 1534-1542. https://doi.org/10.5281/zenodo.16872500
10.5281/zenodo.16872500
