Nanogels are increasingly used in drug delivery systems for their ability to encapsulate a wide range of therapeutic agents and release them in a controlled, targeted manner.
Recent developments have improved their performance by enabling stimulus-responsive release, enhancing tissue penetration, and reducing systemic toxicity. These advances support the use of nanogels as adaptable carriers across various clinical applications.
This article outlines current progress in nanogel research and highlights their potential in next-generation drug delivery.
Image Credit: Gorodenkoff/Shutterstock.com
What Are Nanogels?
Nanogels are three-dimensional, nanoscale hydrogel structures composed of cross-linked polymers that can absorb and retain large amounts of water without dissolving. They can be synthesized from natural or synthetic polymers and tailored for specific applications by adjusting properties such as size, charge, porosity, amphiphilicity, and degradability.
Their hydrophilic structure enhances biocompatibility, making them well-suited for drug delivery. Nanogels can encapsulate a variety of therapeutic agents (including small-molecule drugs, nucleic acids, proteins, and nanoparticles) using electrostatic, van der Waals, hydrophobic, and covalent interactions. This results in higher loading capacities compared to traditional carriers.
Surface functionalization with targeting ligands further improves site-specific delivery, allowing nanogels to accumulate at targeted tissues or cells. Together, these features support their use in controlled and targeted drug delivery with reduced systemic side effects.1
Nanogels Are Like Sponges
Recent Advancements
Cross-Linking Nanogels to Improve Stability and Effectiveness
Recent research has demonstrated that cross-linking strategies, such as functionalizing carrier gels with carboxyl groups for chelation with cisplatin, enhance nanogel stability, drug retention, and therapeutic efficacy.
A study used carboxyl-functionalized dextran (DEX-SA) to adsorb adriamycin hydrochloride, forming polymer micelles (DEX-SA-DOX). In situ cross-linking with cisplatin resulted in cross-linked nanoparticles (DEX-SA-DOX-CDDP), which increased surface charge, prolonged circulation time, and enhanced drug stability.
These cross-linked nanogels demonstrated improved anti-tumor efficacy, reduced toxicity, and optimized biodistribution compared to non-cross-linked nanoparticles or free doxorubicin, highlighting their potential in cancer treatment.2
Novel Materials and Hybrid Nanogels
Recent studies have explored hybrid nanogels that combine natural and synthetic polymers. This approach integrates the biocompatibility and biodegradability of natural macromolecules with the tunable properties and structural stability of synthetic materials.
These systems offer improved drug loading capacity, longer circulation times, and more precise release profiles. By addressing the limitations of single-component nanogels, hybrid formulations enable more reliable delivery while maintaining safety.
Their combined properties are especially useful for delivering complex therapeutics that require specific release kinetics or environmental protection.
Enhanced Drug Release Mechanisms
The development of stimuli-responsive nanogels represents a significant advancement in controlled drug delivery. These “smart” nanogels respond to environmental factors such as pH, temperature, redox potential, or enzyme concentration, allowing for spatially and temporally precise control over drug release.
This feature is particularly beneficial for conditions with a narrow therapeutic window or where localized delivery is crucial to minimize systemic side effects.
For example, pH-responsive nanogels can release their payload in the acidic microenvironment of tumors or within the endosomal compartments of cells, thereby improving therapeutic efficacy and minimizing off-target effects.3
Environmentally Friendly Synthesis of Thermoresponsive Nanogels
A recent study focused on improving control over nanogel synthesis, specifically size, polydispersity, and thermoresponsive behavior. These parameters are essential for ensuring reproducibility and consistent performance in drug delivery.
Researchers used a photo redox-initiating system combined with a tubing flow reactor illuminated by blue LEDs. This method produced environmentally friendly thermoresponsive nanogels based on N-isopropyl acrylamide and N,N′-methylene bisacrylamide. The resulting nanogels had a low polydispersity index (0.231 ± 0.018).
The nanogels encapsulated ciprofloxacin effectively and demonstrated controlled release, colloidal stability, and antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. These findings highlight their potential for antimicrobial and drug delivery applications.4
Breakthrough Clinical Applications
Intravitreal Nanogels for Diabetic Retinopathy Treatment
A study published in the International Journal of Nanomedicine investigated nanogels for intravitreal drug delivery in diabetic retinopathy (DR). The researchers optimized nanogels composed of chondroitin sulfate and low-molecular-weight chitosan to enhance vitreous diffusion, achieving a hydrodynamic diameter under 350 nm and a zeta potential of +15 mV.
In vitro tests confirmed that encapsulating naringenin (NAR) within a β-cyclodextrin inclusion complex (N3@NAR/β-CD) improved encapsulation efficiency, stability, and sustained drug release, indicating the potential for reducing oxidative damage in early-stage DR.5
Transdermal Nanogel Composite for Breast Cancer Therapy
A study published in ACS Applied Materials & Interfaces developed a novel transdermal drug delivery system for controlled doxorubicin (DOX) release in breast cancer therapy.
The nanogel composite, synthesized from β-cyclodextrin-grafted methacrylic acid and hyaluronic acid via controlled radical polymerization, exhibited enhanced drug loading and release efficiency, with a maximum encapsulation of 96.07 % at pH 8.0.
The pH-responsive system facilitated 90 % DOX release at pH 5.5, targeting drug delivery to tumor sites while minimizing systemic toxicity, with extensive evaluations confirming its potential as a non-invasive alternative to conventional chemotherapy.6
Nanogel-Based Targeted Therapy for Urinary Tract Infections
Recently, researchers designed specialized nanogels capable of delivering gentamicin directly to infected bladder cells by incorporating peptides that facilitate cellular uptake.
Preclinical studies showed that this approach enhanced drug penetration, delivering 36 % more gentamicin into infected cells, achieving over 90 % bacterial elimination, and reducing toxicity and antibiotic resistance risk.
The system’s rapid, targeted drug release enabled efficient bacterial eradication. It is now being explored for broader infectious disease applications, including periodontal infections, as a potential alternative to conventional antibiotics that face challenges with tissue penetration and resistance.7
Persistent Challenges
Nanogels face several challenges in drug delivery, including rapid clearance by the mononuclear phagocyte system (MPS), with smaller nanogels undergoing renal filtration and those under 200 nm evading splenic filtration.
Endosomal degradation and premature disassembly during circulation hinder their efficiency in biomolecule delivery, leading to renal clearance. Moreover, passive targeting via the enhanced permeability and retention effect is less effective in hypoxic tumors with poor vasculature. Active targeting also faces limitations, such as heterogeneous receptor expression and off-target accumulation.
Scaling nanogel formulations from laboratory to commercial scale presents challenges in maintaining batch-to-batch reproducibility and cost-effectiveness, as conventional methods are difficult to scale while ensuring consistent properties.
Despite significant developments, controlled drug release remains a challenge, as unpredictable degradation kinetics and burst release effects can lead to premature drug loss and damage to healthy tissues.1,8
Future Outlooks
Researchers are advancing nanogels to improve targeted drug delivery, enhancing their ability to selectively deliver therapeutics to specific cells and reduce toxicity.
For example, recent innovations have focused on surface functionalization techniques, such as the attachment of targeting ligands, to improve the specificity and affinity of nanogels for certain cell types or tissues. This approach has demonstrated improved drug accumulation at the target site while minimizing off-target effects.
Additionally, incorporating multi-functional components into nanogels enables the co-delivery of multiple therapeutic agents, enhancing the overall efficacy of treatments for complex diseases.
Recent developments in nanogel design continue to improve the precision, stability, and bioavailability of advanced drug delivery systems. Ongoing research in this area is expanding the potential of nanomedicine across a wide range of therapeutic applications.1,8,9
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References and Further Reading
- Soni, K. S., Desale, S. S., & Bronich, T. K. (2016). Nanogels: An overview of properties, biomedical applications and obstacles to clinical translation. Journal of controlled release : official journal of the Controlled Release Society, 240, 109–126. https://doi.org/10.1016/j.jconrel.2015.11.009
- Yu, J., Liu, Y., Zhang, Y., Ran, R., Kong, Z., Zhao, D., Liu, M., Zhao, W., Cui, Y., Hua, Y., Gao, L., Zhang, Z., & Yang, Y. (2024). Smart nanogels for cancer treatment from the perspective of functional groups. Frontiers in Bioengineering and Biotechnology, 11, 1329311. https://doi.org/10.3389/fbioe.2023.1329311
- Botha, N. L., Mushonga, P., & Onani, M. O. (2023). Review on nanogels and their applications on dermal therapy. Polymers and Polymer Composites. https://doi.org/10.1177_09673911231192816
- Figueroa, F. N., Torres, J., Campagno, L., Calderón, M., Alovero, F. L., Strumia, M., … & Oksdath-Mansilla, G. (2024). Taming Visible Light-Induced Precipitation Polymerization in Continuous Flow: Developing Thermoresponsive Nanogels for Controlled Antimicrobial Delivery. ACS Applied Engineering Materials, 2(10), 2397-2413. https://doi.org/10.1021/acsaenm.4c00444
- Zucca, G., Vigani, B., Valentino, C., Ruggeri, M., Marchesi, N., Pascale, A., … & Rossi, S. (2025). Chondroitin Sulphate-Chitosan Based Nanogels Loaded with Naringenin-β-Cyclodextrin Complex as Potential Tool for the Treatment of Diabetic Retinopathy: A Formulation Study. International Journal of Nanomedicine, 907-932. https://doi.org/10.2147/IJN.S488507
- Mukkukada Ravi, R., Mani, A., Rahim, S., & Anirudhan, T. S. (2024). A self-skin permeable doxorubicin loaded nanogel composite as a transdermal device for breast cancer therapy. ACS Applied Materials & Interfaces, 16(38), 50407-50429. https://doi.org/10.1021/acsami.4c11373
- Escobedo, H. D., Zawadzki, N., Till, J. K., Vazquez-Torres, A., Wang, G., Simberg, D., Orlicky, D. J., Johnson, J., Guess, M. K., Nair, D. P., & Schurr, M. J. (2025). Nanogels conjugated with cell-penetrating peptide as drug delivery vehicle for treating urinary tract infections. Nanomedicine: Nanotechnology, Biology and Medicine, 65, 102812. https://doi.org/10.1016/j.nano.2025.102812
- S, F., Umashankar, M. S., & Narayanasamy, D. (2024). A Comprehensive Review of Nanogel-Based Drug Delivery Systems. Cureus, 16(9), e68633. https://doi.org/10.7759/cureus.68633
- Attama, A. A., Nnamani, P. O., Onokala, O. B., Ugwu, A. A., & Onugwu, A. L. (2022). Nanogels as target drug delivery systems in cancer therapy: A review of the last decade. Frontiers in pharmacology, 13, 874510. https://doi.org/10.3389/fphar.2022.874510
