K. K. College of Pharmacy, Chennai 600128
Nanosponges are highly porous, three-dimensional nanostructures based on polymers or cyclodextrins, nanosponges combine surface functionality, biocompatibility, and tunable porosity to function as flexible platforms in a variety of applications. This review highlights how modular chemistry allows for the controlled loading and release of a variety of cargos, including small-molecule drugs, peptides, heavy metals, organic pollutants, and imaging agents. It summarizes recent developments in nanosponge design, synthesis, characterization, and application. With a focus on stimuli-responsive and surface-functionalized systems, we analyze formulation strategies in drug delivery that maximize drug-polymer interactions for improved solubility, sustained release, targeted delivery, and decreased toxicity. We assess regeneration strategies, deployment formats, and adsorption mechanisms for environmental remediation that enable the effective removal of heavy metals, dyes, and medications from water streams. Additionally, we investigate cutting-edge biomedical technologies such as antimicrobial coatings and combined therapy (theranostics)
Nanosponges are tiny, sponge-like particles with lots of small holes and tunnels, making them excellent at trapping different substances, including medicines and toxins. These nanocarriers are designed using special polymers, often with a structure based on cyclodextrins, which are naturally occurring sugar molecules that are safely used in drug delivery. Because of their porous nature, nanosponges can hold and transport both water-loving and oil-loving drugs, helping to improve how drugs dissolve, circulate in the body, and target specific disease sites.
In the field of medicine, nanosponges are valued for their ability to release drugs slowly and steadily, which means treatments can work for longer periods of time without frequent dosing. Their structure also protects delicate drugs like proteins or peptides from breaking down too quickly. Scientists are exploring them not only to deliver medicines for conditions like cancer or infections but also for detoxifying dangerous toxins from bacteria or venom by soaking them up before they can cause harm.
Nanosponges aren’t limited to drug delivery. They are also being studied for cleaning up the environment by removing pollutants from water or air, using their absorbent properties to trap harmful chemicals or metals. Their flexible design both the size and the chemistry allows them to be tuned for many tasks, making them a promising tool across medicine, environmental science, and emerging advanced technologies.(1-6)
Fig no1: NANOSPONGES.
IMPORTANCE OF NANOSPONGES:
Advantages:
Disadvantages:
History Background and Evolution:
Advances in nanotechnology, especially since the early 2000s when nanoparticulate drug delivery systems started to receive intense research attention, have fueled the history and evolution of nanosponges as multifunctional nanocarriers. Originally utilizing crosslinked three-dimensional nanoporous structures based on cyclodextrin, nanosponges arose from the intersection of nanomedicine and polymer chemistry. With a strong focus on safety, biodegradability, and minimal toxicity for human use, early research concentrated on their capacity to encapsulate a variety of medications, improve solubility, improve pharmacokinetics, stabilize, and allow for sustained release.
From 2010 to 2015 and beyond, the field grew considerably, encompassing a range of medications such as anticancer agents, polyphenols, and gases of pharmaceutical interest. Smart, stimuli-responsive systems that could release drugs precisely and functionalize with natural ligands to improve active targeting were used in the development of more recent generations of nanosponges. In addition to pharmaceutical applications, nanosponges have played a variety of roles in biotechnology (stabilization of proteins and enzymes, sustained release), food industry innovations (active packaging, flavor modulation), and environmental remediation (e.g., removal of organic pollutants and cleanup of oil spills).
By the late 2010s and early 2020s, nanosponges had developed into a multipurpose platform that combined environmental technologies, cosmetics, and biomedical diagnostics with drug delivery. Their synthesis is still being optimized for industrial scalability and greener practices. Their versatility is found at the intersection of environmental cleanup, multifunctional targeting, sustained drug delivery, and new biomedical applications like diagnostic agents and antiviral treatments. This development demonstrates how nanosponges represent a paradigm shift in nanocarrier systems due to their biocompatibility, controlled drug release, structural versatility and wide range of applications outside of medicine in the environmental and industrial domains. (1,13,14)
Types and Classification of Nanosponges:
Fig no 2:TYPES AND CLASSIFICATION OF NANOSPONGES.
Synthesis and Preparation Methods:
Solvent Method:
Suitable solvents, like dimethylformamide and dimethyl sulfoxide which are polar aprotic solvents, were used in the process. To this, polymer was added and properly blended. The crosslinker/polymer ratio of 8:2 is ideally used into which the above mixture was added. The mixture got from the above mixing, was then left to react for 48 hours and in a temperature range of 10°C and up to solvent’s reflux temperature. On completion of the reaction, the solution was cooled until it reached the room temperature.
Fig no 3:Solvent Method
Ultrasound-Assisted Method:
The ultrasound-assisted method of synthesis utilizes polymer ultrasonic junction. Crosslinking is got without using any solvent, and polymer crosslinking occurs due to ultrasonic waves. In a flask, polymer and crosslinker were combined at a reasonable molar ratio. During the ultra sonication process, ultrasound bath was used to place the flask, at a temperature of 90 °C and for a time period of 5h. The temperature of the collected mixture was reduced after sonication, and the product was split harshly and cleaned to extract unreacted polymer and reagents with an excess volume of water [46]. The washed solid was purified with ethyl alcohol by Soxhlet extraction. The filtered NSs acquired were vacuum dried and processed correctly until further loading of drugs.
Fig no 4:Ultrasound-Associated Method.
Melt Method:
The cross linker and the polymer are melted together in the melting process. All the ingredients were finely homo genized. NSs were collected by washing the acquired product repeatedly with a suitable liquid. Cleaning the product, extracts the waste polymer and reagents which are unreacted and divides the product into the form of NSs [47]. Such blank NSs were further exposed to the encapsulating of narcotics.
Fig no 5:Melt method.
Bubble Electrospinning Method:
A conventional and typical electrospinning configuration consists primarily of a syringe, syringe pump, as defined in many literatures, a high-voltage power, and a grounded collector. But one of the major limitations that limits their applications is the amount of output of nanofibers. In bubble electrospinning, polyvinyl alcohol can also be used as polymer. By addition of distilled water into it, the solution of polymer (10%) was organized, which was then moved at 80–90°C for 2h to obtain a one-phase mixture. It was then left to achieve at room temperature with the polymer solution and then used to prepare nonporous fibres.
Fig no 6: Bubble Electrospinning Method.
Emulsion Solvent Diffusion Method:
Two steps are used in this technique to vary the level of natural and aqueous (ethyl cellulose and polyvinyl liquor). In dichloromethane (20 ml) and an unmistakable measure of polyvinyl liquor added to 150ml of fluid ceaseless process, the scattered stage with ethyl cellulose and moiety is dis solved. At this point, for 2hours at 1000rpm, the blend is thoroughly blended. The required NSs were collected by the filtration method and held for drying in an oven at 40°C for 24h. Dried NSs have been put away in desiccators and the evacuation of remaining solvents is assured. Naproxen sodium NSs using the solvent diffusion method and the diffusion rate was found to be close to 89% of some formulations and the drug loading efficiency to be close to 98%. They also studied the viscosity, particle size, zeta potential, and the stability studies. The Fourier Transform Infrared Spectroscopy (FTIR) results did not indicate any interaction between the drug and excipients. The results also specified high drug loading efficacy and exceptional release profile of drug.
Fig no 7: Emulsion Solvent Diffusion Method.
Quasi Emulsion Solvent Method:
The NSs were arranged in different sums using the poly mer. Using Eudragit RS 100, the inner stage is prepared and added to a fair dissolvable stage. The drug used produced a response and broke down at 35°C under ultra-sonication. As an emulsifying operator, this internal process used in the outside phase containing polyvinyl alcohol goes around. At room temperature, the blend is blended at 1000–2000 rpm for 3h and dried for 12h in an air-warmed oven at 40°C.(1,15)
Fig no 8: Quasi Emulsion Solvent Method.
Physiochemical properties and Characterization Techinques:
Nanosponges are tiny, sponge-like particles made up of special molecules called cyclodextrins that are linked together to form a porous 3D network. Think of them as miniature sponges with many tiny holes—their sponge-like structure helps them hold and carry a wide variety of substances, including medicines. They can trap both water-friendly (hydrophilic) and fat-friendly (lipophilic) drugs, making them very flexible for different treatment needs.
These particles are quite small, typically less than a micrometer in size, and are usually round or spherical. They are stable under heat, able to withstand temperatures up to around 300°C, which means they won’t easily break down during processing or storage. Also, they are biodegradable, which means they break down safely in the body without causing harm. Their surface carries an electrical charge that helps keep them from clumping together when mixed in liquids, keeping them stable and easier to use in different medicines.
One of the most helpful features of nanosponges is their ability to improve the solubility and availability of drugs that don’t dissolve well in water. This makes medicines more effective and helps control how quickly the drugs are released in the body. By tweaking their structure, scientists can even target nanosponges to deliver drugs right where they are needed, reducing side effects and improving treatment outcomes.
Besides medicine, nanosponges also show great promise in cleaning the environment by grabbing and trapping harmful pollutants from water and air. Their reusable nature and strong mechanical properties mean they can work over multiple cycles without losing effectiveness.
In summary, the unique physical and chemical properties of nanosponges make them a powerful tool for both advanced drug delivery and environmental cleanup applications.
CHARACTERIZATION TECHNIQUES:
A comprehensive evaluation of nanosponges includes the following techniques.
Mechanisms of Drug Encapsulation and Release:
The mechanisms of drug encapsulation and release in nanosponges involve their unique three-dimensional, porous, and cross-linked polymeric structure.
Drug Encapsulation Mechanism:
Nanosponges have a mesh-like structure with multiple openings and cavities that can encapsulate drug molecules. The encapsulation is facilitated by physical entrapment, complexation, and interactions between the drug molecules and the nanosponge polymer matrix, often involving host-guest interactions such as hydrogen bonding, van der Waals forces, and hydrophobic effects. Factors influencing encapsulation include the polymer type, degree of cross-linking, drug molecular size and properties (molecular weight, melting point, solubility), and the medium used during formulation. Hydrophilic or hydrophobic characteristics of the nanosponge and drug also play a critical role in encapsulation efficiency.(20)
Fig no 9: Drug Encapsulation Mechanism.
Drug Release Mechanism:
Drug release from nanosponges occurs primarily by diffusion. The active drug is initially encapsulated within the porous structure, and when the nanosponge is introduced into a vehicle (e.g., skin surface or bodily fluids), an equilibrium establishes where the drug diffuses out until the vehicle is saturated. Once applied, the drug release continues as the drug diffuses into the target site (such as the skin or systemic circulation), disrupting equilibrium and resulting in gradual, controlled release. The release rate can be modulated by adjusting the nanosponge’s structural properties, such as cross-linking density and polymer composition. Drug release often follows diffusion-controlled kinetic models like the Higuchi model and can provide sustained release effects, improving bioavailability and reducing dosage frequency.(21)
Fig no 10: MECHANISM OF DRUG RELEASE NANOSPONGES.
Applications in Drug Delivery:
Fig no 11:CYCLODEXTRIN-BASED NANOSPONGES.
1.Targeted Drug Delivery:
Nanosponges can selectively deliver drugs to targeted tissues due to their ability to circulate through the body and bind to specific sites, enhancing drug concentration at the target and reducing systemic toxicity. This targeted release mechanism is useful in cancer treatment and other localized therapies .
2. Controlled and Sustained Release:
The crosslinked network structure of nanosponges permits slow, controlled diffusion of drugs, enabling sustained release over hours to days. This helps maintain therapeutic drug levels for extended periods, reducing dosing frequency and improving patient compliance
3. Solubility and Bioavailability Enhancement:
Nanosponges significantly enhance both solubility and bioavailability of drugs, especially poorly water-soluble drugs, by molecularly encapsulating them within their three-dimensional porous structure. This encapsulation improves drug wetting, prevents crystallinity, and facilitates faster dissolution, leading to enhanced absorption and increased bioavailability.(22)
Application in Environmental remediation:
Nanosponges represent an innovative class of nanomaterials characterized by their highly porous, cross-linked three-dimensional polymeric architecture. These materials have gained widespread attention for environmental remediation due to their efficient adsorption capabilities. Nanosponges can selectively encapsulate and adsorb contaminants including organic dyes, pesticides, heavy metals, phenols, and volatile organic compounds from water and air. Their hydrophilic and hydrophobic domains facilitate complexation with a variety of pollutants through host–guest inclusion, hydrogen bonding, and electrostatic interactions, making them highly versatile for water and air purification technologies. Furthermore, nanosponges can be functionalized or combined with magnetic nanoparticles or other adsorbents to enhance removal efficiency and recyclability. They have shown significant potential in oil spill cleanup by selective affinity towards hydrophobic hydrocarbons and can be integrated into filtration systems for sustainable environmental cleanup .(23,24)
Pollutant Removal:
Nanosponges efficiently remove pollutants across multiple classes:
These pollutant removal capabilities are augmented by facile synthesis methods that allow chemical modification and environment-specific tuning of nanosponges .(25-28)
Water Treatment Technologies:
Nanosponges serve as efficient adsorbents in advanced water treatment systems. Their application in wastewater treatment primarily utilizes adsorption a cost effective, energy-efficient process without the generation of secondary toxic sludge common with other treatment methods. β-Cyclodextrin-based nanosponges dominate research due to their natural origin and structural advantages for pollutant binding. These materials can be deployed in batch or continuous-flow systems including membrane filtration, packed bed adsorption columns, and hybrid technologies combined with photocatalysis or biological treatments. Regeneration and reuse of nanosponges further improve the sustainability of treatment processes .(29,30,31)
Emerging Biomedical Applications:
Biomedical applications of nanosponges are rapidly expanding due to their biocompatibility, high loading capacity, and controlled release properties. Nanosponges have been explored as drug carriers to improve solubility and stability of therapeutic agents. They demonstrate potential in targeted and sustained drug delivery systems, reducing systemic toxicity and enhancing bioavailability. Moreover, nanosponges have been utilized to encapsulate anticancer agents, anti-inflammatory drugs, and diagnostic agents, improving treatment efficacy and minimizing side effects.(32,33,34)
Diagnostic and Therapeutic Uses:
Nanosponges facilitate enhanced biomedical diagnostics by delivering contrast agents or probes selectively. Therapeutically, they enable sustained controlled drug release at target sites, improving clinical outcomes. Nanosponges also mediate detoxification by binding toxins and pathogenic factors in blood or tissues for safer clearance. Their modifiable surfaces cater to multi-functional platforms integrating imaging and therapy, advancing precision medicine.(35,36,37)
Antimicrobial and Antiviral Applications
Nanosponges show promising antimicrobial properties through encapsulation and neutralization of bacterial toxins and viral particles. Surface-engineered nanosponges can trap pathogens and inhibit their interaction with host cells, providing innovative antiviral strategies. This mode of action can overcome drug resistance issues and enhance infection control. Nanosponges have been studied as nano-decoys that absorb viruses before cell infection.(38,39)
Gene and Protein Delivery:
Nanosponges also serve as carriers for gene and protein therapeutics. Their porous structure facilitates loading and protection of nucleic acids or therapeutic proteins from degradation. Controlled release characteristics improve cellular uptake efficiency and therapeutic gene expression. This capability opens avenues in genetic therapy and regenerative medicine by delivering functional biomolecules safely .(40,41,42)
Advanced Functionalization and Stimuli-Responsive Nanosponges:
To expand utility, nanosponges are chemically modified with functional groups or responsive moieties sensitive to stimuli such as pH, temperature, light, or redox conditions. These stimuli-responsive nanosponges enable controlled release or selective adsorption triggered by environmental changes, enhancing specificity and reducing side effects in both environmental and biomedical applications. Magnetic or fluorescent tagging affords facile recovery and monitoring.(43,44,45)
Toxicity, Biocompatibility, and Safety Considerations:
Nanosponges generally exhibit good biocompatibility and low toxicity, especially those derived from biopolymers like cyclodextrins or keratin. However, comprehensive toxicity evaluations involving cell viability, immunogenicity, and in vivo studies are critical. Surface chemistry, size, and dose affect biological interaction profiles, necessitating tailored designs to ensure safety for clinical translation and environmental release.(46,47)
Challenges in Clinical and Commercial Translation:
Nanosponges, despite their promising characteristics such as porous architecture, biocompatibility, and drug encapsulation versatility, face several hurdles in clinical and commercial adoption. Primary challenges include the potential nanotoxicity and long-term safety concerns that demand rigorous evaluation of biodistribution, metabolism, and excretion. There are technical difficulties in large-scale synthesis maintaining reproducibility, structural stability, and consistent quality control for regulatory approval. Regulatory frameworks are still evolving, and robust standardized protocols for characterization and safety are required. Manufacturing costs, scalability, and translation of laboratory synthesis methods to cost-effective industrial production also remain considerable barriers.(46)
Future Perspectives and Research Directions:
Harmacology, and clinical studies will drive advancements in nanosponges. Future efforts are expected to focus on optimizing nanosponges' design for specific therapeutic applications by improving polymer-crosslinker chemistry and functionalization to enhance target specificity and controlled release profiles. Integration of diagnostic and therapeutic functions (theranostics) to enable real-time tracking and personalized treatment is a growing trend. Environmentally friendly, cost-effective, and sustainable synthesis processes will be prioritized. Expanding applications beyond drug delivery to environmental remediation, biosensing, gene delivery, and vaccine carriers offer broader utility. Additionally, addressing nanotoxicity by developing biodegradable or biocompatible frameworks and performing comprehensive in vivo safety studies are crucial. Continued interdisciplinary research combining materials science.
CONCLUSION:
Nanosponges represent a flexible and multifunctional nanocarrier platform with immense potential in drug delivery, environmental protection, and emerging biomedical fields. Their unique porous structure allows loading diverse bioactive agents with controlled release, improving therapeutic efficacy and reducing side effects. While current challenges related to safety, scalability, and regulatory approval slow clinical translation, ongoing research promises to overcome these hurdles. As understanding and technology evolve, nanosponges are poised to expand their role as smart, targeted carriers driving advances in personalized medicine and environmental health.
ACKNOWLEDGEMENT:
We sincerely thank our Management, Dr. A. Meena, Principal, and Dr. A. Shanthy, vice Principal, for their encouraging and support for this review work.
CONFLICTS OF INTEREST:
The authors state that there are no conflicts of interest.
REFERENCES
Bhuvaneswari K, Sathish Kumar D, Dhanalakshmi P, Kumara Guru V, Nanosponges: Multifunctional Nanocarriers at the Interface of Drug Delivery, Environmental Remediation, and Emerging Biomedical Technologies, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 10, 1308-1322. https://doi.org/10.5281/zenodo.17342035
10.5281/zenodo.17342035
