A Review: Nanosponge Drug Delivery System

Abstract

The nanosponge drug delivery system has emerged as a revolutionary approach in pharmaceutical nanotechnology, offering significant improvements in drug solubility, stability, and bioavailability. These porous, nano-sized carriers (typically ranging from 10–1000 nm) are composed of hyper-cross-linked polymers such as cyclodextrins, polyesters, or polyamales, forming a three-dimensional network capable of entrapping both hydrophobic and hydrophilic drugs. Their unique structural properties enable controlled, sustained, and targeted drug release, minimizing side effects and enhancing therapeutic efficacy. Nanosponges are particularly advantageous for poorly water-soluble drugs (BCS Class II & IV), protecting them from chemical degradation, enzymatic hydrolysis, and pH variations. They can be engineered for various administration routes, including oral, topical, transdermal, ocular, and pulmonary delivery. Recent advancements explore stimuli-responsive nanosponges that release drugs in response to pH, temperature, or enzymes, as well as hybrid nanosponges combined with liposomes or nanoparticles for multifunctional applications. This review comprehensively discusses the fabrication techniques (e.g., emulsion solvent diffusion, ultrasound-assisted synthesis), characterization methods (DLS, SEM, BET analysis), and biomedical applications (cancer therapy, antiviral delivery, protein encapsulation). Despite their potential, challenges such as scalability, long-term toxicity, and regulatory approval remain. Future research focuses on personalized nanosponge formulations and clinical translation, paving the way for next-generation drug delivery systems.

Introduction

Nanosponges are nano-sized, porous carriers formed by cross-linked polymers (often cyclodextrins), capable of encapsulating a wide range of therapeutic agents including poorly soluble drugs, proteins, and genetic materials. They enable controlled drug release, targeted delivery, and protection from degradation, addressing key pharmaceutical challenges.

2. Composition:
Key components include:

• Polymers: Cyclodextrins, PVA, PLGA, etc.

• Cross-linkers: DPC, CDI, pyromellitic anhydride.

• Active Drugs: Hydrophilic or hydrophobic drugs entrapped in the matrix.

• Solvents/Modifiers: DMF, DMSO; PEG or ligands for targeting.

3. Preparation Methods:

• Emulsion Solvent Diffusion: Simple, scalable.

• Ultrasound-Assisted Synthesis: Enhances cross-linking and reduces size.

• Solvent Method: Direct cross-linking under reflux.

• Quasi-Emulsion Diffusion: Optimized for hydrophobic drugs.

4. Characterization Techniques:

• Size & Surface Charge: DLS, zeta potential.

• Morphology: SEM, TEM.

• Surface Area: BET analysis.

• Drug Encapsulation: HPLC, UV-Vis.

• Release Kinetics: In vitro testing.

• Thermal & Chemical Properties: DSC, TGA, FTIR, XRD.

5. Advantages:

• Improves solubility and bioavailability.

• Allows controlled/sustained and stimuli-responsive release.

• Enhances drug stability and targeting.

• Compatible with a wide range of drugs and delivery routes.

• Demonstrates low toxicity and biocompatibility.

6. Applications:

• Cancer therapy: Targeted and responsive delivery of chemotherapeutics.

• Topical/transdermal delivery: Enhanced skin penetration.

• Oral, ocular, pulmonary delivery: Improved retention and absorption.

• Biologics & gene delivery: Protection and controlled release of proteins/siRNA.

• Antiviral strategies: Virus-neutralizing nanosponges for diseases like COVID-19.

7. Recent Advances:

• Stimuli-responsive systems (pH, temperature, enzyme).

• Hybrid nanosponges (e.g., liposome or gold-nanoparticle conjugates).

• Antiviral/bacterial coatings, 3D-printed scaffolds, and brain-targeting modifications.

8. Challenges & Future Directions:

• Scale-up difficulties, regulatory hurdles, and long-term safety are key barriers.

• Future efforts should focus on:

  • Enhancing reproducibility and cost-effectiveness.

  • Developing personalized medicine applications.

  • Green synthesis approaches.

  • Stronger collaboration between academia, industry, and regulators.

Conclusion

Nanosponges represent a breakthrough in drug delivery, offering improved drug stability, bioavailability, and targeted release. With ongoing research, they hold immense potential for treating various diseases, including cancer, infections, and neurological disorders. Future advancements in polymer science and nanotechnology will further expand their applications.

References

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Copyright © 2025 Mr. Aditya Kanchan, Ms. Rekha Kolpe, Mr. Nitin Gawai. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.