INTRODUCTION TO NANO SPONGES:

Recent advances in nanotechnology have led to the development of targeted drug delivery systems. However, achieving precise molecule delivery demands specialized strategies. Nano sponges have emerged as a promising solution, addressing challenges like drug toxicity, poor body absorption, and controlled release. They efficiently transport both water-soluble and water-insoluble drugs.¹ The medical field has struggled with precise drug delivery and controlled release. Nano sponges, novel molecules, offer a solution. These tiny structures, virus-sized, carry diverse drugs.

Available in oral, parenteral, topical, or inhalable forms, they navigate the body to target locations (As shown in Figure 1). Once there, they adhere and gradually release medicine. Nano sponges are solid, porous particles capable of encapsulating active ingredients in their nanocavities.²

Figure: 1 Structure of Nano-sponges

[Source:https://www.intelligentliving.co/nanosponges-bloodstream]

Nano sponges are advantageous carriers for enzymes, proteins, vaccines, and antibodies, optimizing drug delivery. Precision release at targeted sites boosts effectiveness while minimizing side effects by improving solubility and bioavailability. These versatile structures can be synthesized for oral, topical, or parenteral use, particularly benefiting low bioavailability drugs.³ Constructed from biodegradable polyester, Nano sponges' 3D designaids-controlled breakdown. Polyester's gradual degradation within the body liberates encapsulated drug particles. These Nano sponges securely retain drugs using diverse methods, distinct from conventional nanoparticles. They remain solid, resisting dissolution in water or organic solvents, adaptable as oral, parental, topical, or inhalable doses.

Researchers have utilized Nano sponges for proteins, peptides, genes, anticancer agents, and biomolecules, heightening effectiveness and diminishing adverse reactions. Alternately, excipients, lubricants, diluents, and anti-caking agents facilitate capsule and tablet production. Sterile water or suitable solutions are used for parenteral administration.^4,5

Ideal Characteristic of Nano Sponges:

· Nano sponges have advantages in terms of size (1m or less) and the ability to adjust cavity polarity.

· Specific sizes of nano sponges can be synthesized by varying the cross linker-to-polymer ratio.

· They exhibit either para crystalline or crystalline forms based on the process conditions, which is crucial in drug complexation.

· Nano sponges are non-toxic, non-porous, and insoluble in most organic solvents, remaining stable up to 300°C.

· They maintain stability within a pH range of 1 to 11 and form opalescent and clear suspensions in water.

· Nano sponges can be reproduced through thermal desorption, solvent, and microwave extraction.

· Their 3D structure enables them to capture, transport, and selectively release various substances.

· They can be targeted to different sites by connecting with specific functional groups using chemical linkers.

· Nano sponges form inclusion and non-inclusion complexes with various drugs, and magnetic properties can be added by introducing magnetic particles into the reaction mixture.

· Nano sponges are designed to encapsulate poorly water-soluble drugs and are aqueous-soluble, porous particles.

· They can transport both lipophilic and hydrophilic drugs while protecting them from physicochemical degradation.

· Additionally, they can remove organic impurities from water.⁶

Advantages of Nanosponges:

· Improve stability, elegance, and flexibility of formulations.

· Reduce side effects by entrapping ingredientsandincorporate immiscible liquids effectively.

· Enable extended release over 12-24 hours.

· Enhance solubility of poorly water-soluble drugsand act as a self-sterilizer with tiny pores.

· Enhance compliance by minimizing side effects and dosing frequency.⁷

· Mask flavors facilitate the transition from liquid to solid forms while also assisting in detoxifying the body.¹

Disadvantages of Nano Sponges:

· Nano sponges primarily engage with small particles and struggle with larger atoms.

· They are restricted to incorporating very small atoms and molecules.

· Loading capacity hinges on formulation nature (para crystalline or crystalline), heavily influenced by crystallization.

· Their structural limitations prevent accommodation of larger molecules, confining them to encapsulating small ones.^8,3

Classification of Nano Sponges⁹

The various types of nano sponges are enlisted as under

Significance of Nanosponges:

· Nano sponges are safe and biodegradable, posing no irritation or toxicity.

· Adjustable size via cross-linker to polymer ratio change.

· Carry lipophilic and hydrophilic drugs, ensuring protection and controlled release.

· Provide stable, flexible, and elegant formulations with extended, predictable 12–24-hour release.

· Improve solubility for both water-soluble and poorly water-soluble substances.

· Serve as nano carriers in biomedical applications and convert liquids to solids with mask flavors.

· They remain stable within a pH range of 1-11.¹⁰

Compostion of Nanosponges:

To produce Nano sponges, a combination of polymer-cyclodextrin, and crosslinker is employed, as depicted in Figure 2.¹¹

Polymer: Nano sponges are synthesized from diverse polymer materials, selected according to the intended cavity size, and carried drug molecules. Choosing the right polymer is vital for achieving the desired drug release and sponge structure. Essential ligands must attach to the chosen polymer for precise drug delivery.¹²

Cross-linking agent: Cross-linking agents such as diphenyl carbonate, dichloromethane, dialkyl carbonates, and di-isocyanates can be selected based on the polymer structure and drug formulation requirements.

Drug substance: The drug molecule needs to fall within a molecular weight range of 100 to 400 Daltons and have a structure with fewer than five condensed rings. It should display minimal solubility of less than 10 10MG/ML and demonstrate a melting point range below 250°C.¹³

To make Nano sponges, scientists use different types of materials called polymers and cross-linkers. The specific kinds of polymers and cross-linkers used can be found in a table labeled "Table 1.1." This table provides information about the different types of polymers and cross-linkers that are used to create Nano sponges.

Figure2: formationofcyclodextrin

[Source: https://ars.els-cdn.com/content/image/1-s2.0-S0144861717306112-fx1_lrg.jpg]

Table 1.1: Chemicalsused for synthesis of Nano-sponges¹⁴

Polymers	Crosslinkers
Hypercross-linkedPolystyrenes	Carbonyldiimidazoles
Cyclodextrins and its derivatives like Methyl β-Cyclodextrin	Carbonyldiimidazoles
Alkyloxycarbonyl Cyclodextrins	Diarylcarbonates
2-HydroxyPropylβ-Cyclodextrins	Di-isocyanates
Copolymers like Poly (Valerolactone-ally lvalerolactone)	Pyromellitic anhydride, Epichloridrine, Glutaraldehyde
Poly (Valerolactone-ally Dvalerolactone oxepane dione)	Carboxylicaciddianhydrides
Ethyl Cellulose	2,2-bis(acrylamide) Aceticacid
PVP	Dichloromethane

Methods of Nano Sponges:

Process of arrangement: following methods are used for the preparation of nano sponges.

Melt technique:

The melt method employs the appropriate cross-linker to react with cyclodextrin. The reaction mixture is then placed in a preheated 250mL flask at 100°C and allowed to react for five hours using a magnetic stirrer. Afterward, the mixture is advised to cool before breaking down and rinsing the final product with a suitable solvent to remove any remaining impurities, as shown in the figure 3.

Figure 3: Nano-spongesbymelt technique

Solvent diffusion method:

Emulsion solvent diffusion technique:

This approach involves the use of separate volumes of organic and aqueous phases. The organic phase contains a combination of drug and polymer, while the aqueous phase contains poly vinyl alcohol [PVA]. The drug and polymer are dissolved in an appropriate organic solvent and slowly added to the aqueous phase. The mixture is then stirred with a magnetic stirrer at 1000rpm for two or more hours, as depicted in the figure 4 below. After filtration and washing, the final nanosponges (NS) are formed. They are subsequently air-dried at room temperature or vacuum dried at 40°C for 24hours.¹⁵

Figure 4: Nano-spongesbysolventdiffusionmethod

Quasi-Emulsion solvent diffusion:

In this process, the first stage involves dissolving the polymer in a suitable solvent through diffusion. At 35°C, the polymer solution is mixed with the medication using ultrasonic waves. Next, the inner phase is poured into the outer phase, which consists of a mixture of PVA and water. The resulting suspension is stirred with a magnetic stirrer for 60minutes at 1000rpm. After the generation of Nano Sponges, they are filtered and dried in a hot air oven at 40°C for two hours.^16,17

Solvent method:

Mix the polymer with a suitable polar solvent and add it to the mixture, preferably with a crosslinker/polymer molar ratio ranging from 4 to 16. Allow the reaction to proceed for 1 to 48 hours at a temperature between 100°C and the solvent's reflux temperature. Carbonyl compounds such as diethyl carbonate and carbonyl di imidazole are commonly used as crosslinkers. Once the reaction is complete, cool the solution and add a large amount of bi-distilled water. Subsequently, filter the product under vacuum and purify it using an extended Soxhlet process.¹⁸

Ultrasound assisted synthesis:

Sonication is used to interact crosslinkers and polymers without a solvent. The polymer and crosslinker are combined in a flask, heated to 90°C, and sonicated for five hours in a water-filled ultrasonic bath. After cooling, the unreacted polymer is washed away with water. The product is then purified using an extended ethanol Soxhlet extraction and vacuum dried at 250°C. The process produces hyper-crosslinked cyclodextrin, which can be used to create nano sponges for drug delivery. Nano sponges typically have a diameter smaller than 1 micron, with the option to select fractions as small as 500 nanometers.¹⁹

Polymerization method:

A non-polar drug solution is combined with the monomer to create a mixture, and then an aqueous phase is introduced, typically containing surfactant and dispersant to improve suspension. Polymerization leads to the formation of reservoirs with open pores on the surface. After obtaining the desired size discrete droplet suspension, catalysis or temperature elevation is employed to activate the monomers.³

Microwave assisted synthesis:

Microwave irradiation is a rapid and efficient method for creating cyclodextrin nano sponges. These nano sponges exhibit higher crystallinity compared to other methods. Microwave-assisted synthesis shows a fourfold reduction in reaction time compared to conventional heating methods, resulting in homogeneous particle distribution and uniform crystallinity.¹¹

Drug Loading:

To attain a particle size below 500 nm, nanosponges require pre-treatment. Preventing aggregation involves suspending in water, sonication, and subsequent centrifugation to isolate the colloidal fraction, followed by freeze-drying. For drug complexation, excess drug is stirred with an aqueous nanosponge suspension. After complexation, uncomplexed drug is separated by centrifugation, yielding solid nanosponge crystals through solvent evaporation. The nanosponges' crystalline structure notably impacts drug complexation, with higher loading capacity in crystalline nanosponges compared to paracrystalline ones. Poorly crystalline nanosponges result in a mechanical mixture rather than an inclusion complex during drug infusion.^20,15

Figure 5 Drug loading in nano sponges

[source: https://www.researchgate.net/figure/Fig-4-Drug-loading-in-nanosponge-A-higher-resolution-colour-version-of-this-figure_fig4_344091923/download]

Mechanism of Drug Release:

The Nano sponge-based formulation, composed of a polymer and crosslinker, can be delivered in encapsulated forms, such as injections, creams, or lotions applied to the skin. This formulation permeates through the small pores of the skin (As shown in Figure 6), reaching the bloodstream and binding to the cellular components of red blood cells. This interaction facilitates the targeting of specific cells, thereby achieving the intended pharmacological action.

Figure 6: Mechanism of drug release of encapsulated nanosponge²¹

[sources: https://www.longdom.org/open-access/a-novel-revolutionary-approach-of-a-synthesis-and-application-of-targeted-nanosponge-drug-delivery-81331.html]

Factor affecting Preparation of Nano Sponges²²

Temperature:

Variations in temperature can disrupt the complexation between the drug and nanosponges. An increase in temperature may weaken the interaction forces between the drug and nanosponges, leading to a decrease in the stability constant of the drug/nanosponges complex.

Type of drug:

The drug must have a molecular weight between 100 and 400 Da, with a condensed ring containing up to 5 atoms. It should dissolve in water at less than 10mg/ml and melt below 250°C.

Type of polymer:

The polymer selection notably impacts Nano Sponges' hydroxylated characteristics. Hydroxypropylated IB-CD exhibits a more favorable tendency for forming addition complexes compared to α, β, and γ-cyclodextrins.

Degree of substitution:

The type, quantity, and arrangement of substitutions on the parent molecule can profoundly impact the complexation capability of nano sponges.

Characterization and Evaluation of Nano Sponges:

Particle size determination:

During nanosponge production, precise particle size is maintained, ensuring smooth flow and appealing appearance of powders. Special equipment such as laser light and tools like a Malvern zeta sizer are used for measurement. Impact on drug release is studied through graphs illustrating size changes over time. For skin medication delivery, particles of 10 to 25 micrometers are preferred, as larger ones over 30micrometers could feel rough on the skin.¹⁹

Morphology and surface topography:

In the context of nano sponge preparation, morphological investigations involve the deposition of gold palladium into the samples under an Argon atmosphere at room temperature. The surface structure is subsequently examined using scanning electron microscopy.

Determination of true density:

The true density of nanoparticles and benzoyl peroxide can be calculated using a method known as repeated mean determination, which involves measurements conducted using an ultra-cymometer under a helium gas atmosphere.²¹

Thin layer chromatography:

Thin layer chromatography (TLC) effectively decreases the retention factor (RF values) of drug molecules, leading to a substantial reduction. This alteration facilitates the detection and localization of the complex formed between the drug and the nano sponges.²⁴

Thermo analytical method:

Using thermo-analytical methods, we can detect changes in drug compounds before degradation occurs due to interactions with Nano Sponges. Drug substances might undergo melting, evaporation, decomposition, oxidation, or polymorphic transitions when complex formation takes place. Weight loss, observed in DTA and DSC thermograms, can indicate inclusion complex formation, evident through peak shifts, broadening, and the appearance or disappearance of peaks.¹⁴

Microscopic studies:

Utilizing electron microscopy, the disparity in crystalline characteristics between the raw constituents and the resultant product serves as an indicative marker of the product/complex formation. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) are viable methods for investigating the microstructural attributes of the drug, nanosponges, and the ultimate product.²⁵

Solubility studies:

By scrutinizing the nanosponges and their impact on drug solubility, Higuchi and Connors introduced a phase solubility method to investigate the formation of inclusion complexes.²⁶

Infrared spectroscopy:

IR spectroscopy is employed to analyze interactions between drug molecules and nanosponges in their solid forms. Some changes are observed in nanosponge bands during complex formation. When the guest molecule comprises less than 25% of the total, the nanosponge bands can mask those of the included portions. Compared to other methods, this approach is less effective in detecting inclusion complexes. Infrared spectral studies provide insights into hydrogen interactions in various functional groups, including carbonyl and sulfonyl bands. However, it's restricted to drugs with such characteristic bands. The absorbance band shift to lower frequencies, accompanied by increased intensity and broadening due to stretching vibrations in hydrogen bond formation groups, is particularly pronounced at the hydroxyl group.²⁶

Loading efficiency:

To quantify the loading efficiency, UV spectrophotometry and liquid chromatography techniques can be employed to assess the quantity of drug encapsulated within the Nano Sponges. The loading efficiency of the Nano Sponges can be determined using the subsequent equation.¹

Acrual drug content

Loading = ------------------------------ × 100 …….(1)

of giciency Theoretical drug content

Production yeild:

To calculate the production yield, one needs to determine both the weight of the starting raw materials and the weight of the final permanent nanosponges.¹⁴

Practical mass of nanospondes

Product yeild = -------------------------------- × 100 …. (2)

Theoretical mass

Zeta potential:

An extra electrode can be incorporated into particle size instrumentation to assess zeta potential, a parameter indicative of surface charge.²⁶

Determination of entraptment efficiency:

An equivalent amount of Nano Sponges corresponding to 100mg of the drug was pulverized into powder and subsequently placed into a 100ml volumetric flask containing 10ml of methanol. The flask was then filled up to the mark with simulated gastric fluid of pH 1.2. After a 24-hour period, the solution was filtered using Whatman filter paper, and the absorbance was measured through spectrophotometric analysis following appropriate dilution.²⁷

Application Used For Nanosponges:

Nanosponges in protein drug delivery:

Bovine Serum Albumin (BSA) protein is prone to instability in solution and is therefore preserved in a lyophilized state. The utilization of swellable cyclodextrin-based Poly [amidoamine] nanosponges has shown to improve the stability of proteins, such as BSA. Nanosponges have been employed for various purposes including enzyme immobilization, protein encapsulation, and subsequent controlled release and stabilization.

Cancer:

In cancer patients, drug effectiveness is often hindered by difficulty in reaching tumors and immune system interference. Nanosponges are emerging as a solution. They encase drugs, like paclitaxel, for targeted delivery. Nanosponges effectively treat both slow-growing breast cancer and fast-spreading mouse glioma. Compared to other chemotherapy, nanosponges perform better in eradicating cancer cells and slowing tumor growth. These nanoparticles gradually release anticancer drugs as they degrade. Peptide linkers, designed to adhere to cancer cells, enhance targeting.²⁸

Nanosponges as chemical sensors:

Nano sponges, a class of metal oxides, can serve as chemical sensors for the detection of hydrogen using exceptionally sensitive techniques. The inherent structure of the nanosponge, characterized by initial absence of contact, facilitates unhindered electron transfer, leading to enhanced 3D interconnectivity. This intricate network renders nanosponges significantly sensitive to oxygen.²⁷

Oxygen delivery system:

Utilizing a Nano sponge/hydrogel system, silicone membranes can be employed to facilitate oxygen permeation. These membranes, suspended in water, become saturated with moisture. Furthermore, they hold potential for addressing hypoxic tissues arising from diverse pathological conditions.²⁹

Solubility enhancement:

Many pharmaceuticals suffer from poor water solubility, limiting their development and clinical use. Nano sponges can help by enhancing solubility and wetting of poorly soluble molecules, improving drug delivery. This approach addresses formulation and bioavailability issues, making drugs more effective.³⁰

Protection from light or degradation:

Beyond safeguarding encapsulated molecules against light-induced, chemical, and enzymatic degradation, nanosponges also contribute to sustaining their potency through the preservation of stability.

Antiviral application:

Nanosponges allow ocular, nasal, and pulmonary administration. Nano carriers enable targeted delivery of antiviral drugs and small interfering RNA (siRNA) to nasal epithelia and lungs, effectively combating infections caused by respiratory syncytial viruses, influenza viruses, and rhinoviruses. The nano delivery system also facilitates the transportation of zidovudine, saquinavir, interferon-α, and acyclovir to target HIV, HBV, and HSV infections.¹⁹

Topical agents:

This specialized delivery system provides controlled and prolonged release of topical drugs on the skin. Formulated as topical nanosponges, it minimizes adverse effects caused by active ingredient penetration, ensuring steady drug release for effectiveness without irritation. Various product forms, including gels, lotions, creams, ointments, liquids, and powders, can be created using this technology.⁶

Sustain delivery system:

Modified-release formulations are strategically designed to achieve objectives such as dose reduction, modulation of pharmacokinetic patterns, and mitigation of adverse effects by orchestrating gradual and continuous drug release throughout the therapeutic regimen. Nano sponges, characterized by their encapsulation capabilities, exhibit the ability to sustain the release of volatile compounds, including essential oils. This is achieved through the integration of appropriate polymers and crosslinking agents, enabling the prolonged retention and controlled extension of the release of these volatile substances.

Oral delivery system:

The absorption kinetics and extent of hydrophobic drugs are governed by the dissolution kinetics of the drug itself. This dissolution phase plays a pivotal role in influencing the oral bioavailability. Consequently, the encapsulation of numerous hydrophobic drugs within a matrix comprising excipients, diluents, and lubricants often results in incomplete absorption from the gastrointestinal tract.

Topical delivery system:

Traditional skincare items often pack high active ingredient levels briefly, causing fluctuating over- and under-dosing. Absorbing substances directly through the skin can lead to issues like rashes. The gradual release method preserves effectiveness and minimizes discomfort. Nano sponges, suitable for gels, creams, lotions, and powders, boost skin absorption. When included in topical gels or creams, they might improve solubility on the skin surface and enhance functionality.

Protein delivery:

An innovative approach was used to create expandable cyclodextrin-based nano sponges for protein delivery. New swellable poly-amidoamine nano sponges (PAA-NS) were synthesized by linking cyclodextrin with either 2,2-bis (acrylamidoacetic acid) or a truncated polyamide-amine chain formed by 2,2-bis and 2-methylpiperazine. These PAA-NS were then transformed into Nano suspensions using high-pressure homogenization. The swelling behavior of these nano sponges was found to vary with the pH of the surrounding medium.

Gas delivery:

Certain gases can be stored in nano sponge formulations, benefiting biomedical applications. Gas complexation within nanosponges, including oxygen and carbon dioxide, holds potential for medical contexts. Nano Sponges can encapsulate notable amounts of carbon dioxide, 1-methyl cyclopropene, and oxygen. Oxygen-filled nanosponges have potential medical applications. By cross-linking cyclodextrin nanosponges with carbonyl diimidazole, distinct oxygen-encapsulating formulations were achieved. Oxygen release from the Nano sponges was facilitated using a nano sponge/hydrogel combination method, regardless of ultrasound presence.³

Nanosponge in Enzyme immobilization:

Nanoscale technology is commonly employed for enzyme stabilization. CD-NS, compared to CDs, displays notably higher inclusion constants, making them suitable for enzyme immobilization. Immobilized enzymes exhibit improved stability and catalytic efficiency, simplifying product separation and recovery. This strategy also boosts biocatalyst's thermal and operational stability. Boscolo et al. explored the potent catalytic activity of diverse lipases from Pseudomonas fluorescens absorbed onto cyclodextrin-based Nano Sponges. Various industrial applications, such as triacylglycerol hydrolysis and lipase-catalyzed trans-esterification processes, are implicated.

Nano sponge has a carrier for biocatalyst:

Nanosponges find utility in delivering proteins and other macromolecules, encompassing enzymes, vaccines, proteins, and antibodies, particularly for diagnostic applications. Cyclodextrin-based ultrafine particles envelop the surface of the encapsulated proteins and macromolecules intended for delivery.¹³

Encapsulation of gases:

A carbonate nanosponge based on cyclodextrin was utilized to create inclusion complexes with three different gases: oxygen, carbon dioxide, and 1-methyl cyclopropene. Gas complexation, particularly with oxygen or carbon dioxide, shows promise in various biomedical applications. Notably, the oxygen-loaded nanosponge could potentially target tissues with low oxygen levels seen in various disorders. Additionally, due to its highly porous structure, Nano Sponges have been investigated as effective gas carriers. The nanosponge formulation exhibits controlled storage and release of oxygen. In the future, these nanosponges could be valuable for delivering crucial gases.¹⁹

Removal of organic pollutants from water:

Combining ceramic porous filters with insoluble beta-cyclodextrin nano sponges yields a hybrid organic/inorganic filter module. These nano sponges effectively capture organic pollutants from water, elevating water purification efficiency. Trials exhibited over 95% removal of polycyclic aromatic hydrocarbons (PAHs). Research into Nano sponge formulations for drug purposes has demonstrated their potential in eliminating pollutants like trihalogenomethanes (THMs), nonaromatic hydrocarbons (BTX), and pesticides (simazine).⁶

CONCLUSION:

In conclusion, this review article has focused on the pivotal role of Nano sponges as a controlled drug release mechanism targeting specific sites. The unique combination of small dimensions and spherical morphology in these delivery systems facilitates the creation of diverse dosage forms, including parenteral, aerosol, topical, and oral formulations, tailored to precise requirements using advanced techniques. This innovative technology not only captures active ingredients effectively, but also mitigates side effects, enhances stability, augments aesthetic appeal, and bolsters formulation versatility. As a result, it offers a specialized approach to drug delivery, prolonging dosing intervals and thereby promoting improved patient adherence. Considering the manifold challenges in the realm of pharmaceutical nanotechnology, Nano sponge formulations emerge as a promising solution, poised to address a spectrum of nano-related concerns.

REFRENCES:

1. Bhowmik H, venkatesh DN, Kuila A, Kumar KH. Nanosponges: a review. 2018; 10(4): 3–7.

2. Kimbonguila A, Matos L, Petit J, Scher J, Nzikou JM. Effect of physical treatment on the physicochemical, rheological and functional properties of yam meal of the cultivar “ngumvu” from dioscorea alata l. of congo. Int J Recent Sci Res. 2019; 10(c): 30693–5.

3. Bilal J. S, Abhishek S. P, Ankush S. B, Indrayani D. R, Manojkumar M. N. Nanosponges: an evolutionary trend for targeted drug delivery. Int J Pharm Sci Med. 2021; 6(6): 1–14.

4. Alongi J, Poskovic M, Frache A, Trotta F. Role of cyclodextrin nanosponges in polypropylene photooxidation. Carbohydr polym [internet]. 2011; 86(1):127–35. : http://dx.doi.org/10.1016/j.carbpol.2011.04.022

5. Pawar AY, Naik AK, Jadhav KR. Nanosponges: a novel drug delivery system. Asian J Pharm. 2016;10(4):s456–63.

6. Ghurghure SM, Sana M, Pathan A, Surwase PR. Nanosponges: a novel approach for Targeted Drug Delivery System. 2018;15–23.

7. Tejashri G, Amrita B, Darshana J. Cyclodextrin based nanosponges for pharmaceutical use: a review. 2013; 63: 335–58.

8. Muni Raja Lakshmi K, Suma Shree C, Lakshmi Priya N. Nano sponges: a novel approach for targeted drug delivery systems. J Drug Deliv Ther. 2021; 11(2): 247–52.

9. Pawar S, Shende P, Trotta F, Shende P, Trotta F. Accepted manuscript. 2019;

10. Jyoti P, Tulsi B, Popin K, Chetna B, Jyoti P. An innovative advancement for targeted drug delivery : nanosponges. 2016; 6(2): 59–64.

11. Sherje AP, Dravyakar BR, Kadam D, Jadhav M. Cyclodextrin-based nanosponges: a critical review. Carbohydr polym [internet]. 2017; 173(1): 37–49. Available from: http://dx.doi.org/10.1016/j.carbpol.2017.05.086

12. Yadav RP, Sheeba FR. Nanosponges - overview. Asian j pharm technol [internet]. 2022 mar 5 [cited 2023 aug 8];12(1):76–76. Available from: https://ajptonline.com/abstractview.aspx?pid=2022-12-1-12

13. Ravi SC, Krishnakumar K, Nair SK. Nano sponges: a targeted drug delivery system and its applications. Gsc Biol Pharm Sci. 2019; 7(3): 40–7.

14. Article R, Bachkar BA, Gadhe LT, Battase P, Mahajan N, Wagh R, et al. Nanosponges: a potential nanocarrier for targeted. 2015; 4(3): 751–68.

15. Sadhasivam J, Sugumaran A, Narayanaswamy D. Nano sponges: a potential drug delivery approach. Res J Pharm Technol. 2020; 13(7): 3442–8.

16. Kaur S, Kumar S. Nanosponges: An innovative drug delivery system. 2019;12.

17. Pravin P, Adhikrao Y, Varsha G. Different techniques for preparation of nanosuspension with reference to its characterisation and various applications - a review. Asian J Res Pharm Sci. 2018; 8(4): 210–6.

18. Penjuri SCB, Ravouru N, Damineni S, BNS S, Poreddy sr. Lasoprazol yüklü nanosüngerlerin formülasyonu ve değerlendirilmesi. Turkish J Pharm Sci. 2016; 13(3): 304–10.

19. Bolmal UB, Manvi F V, Kotha R, Palla SS, Paladugu A, Reddy KR. Recent advances in nanosponges as drug delivery system. Int j Pharm Sci Nanotechnol. 2013; 6(1): 1934–44.

20. Chilajwar S V, Pednekar PP, Jadhav KR, Kadam VJ. Cyclodextrin-based nanosponges: a propitious platform for Enhancing Drug Delivery. 2014; 111–20.

21. Vishwakarma A, Nikam P, Mogal R, Talele S. Review on nanosponges: a benefication for novel drug delivery. 2014; 6(1): 11–20.

22. Panda S, Vijayalakshmi S, Pattnaik S, Swain RP. Nanosponges: a novel carrier for targeted drug delivery. Int J Pharmtech Res. 2015; 8(7): 213–24.

23. Satishs. Sathish Kumar GM. Asian Journal of Pharmacy and technology [internet]. [cited 2023 aug 8]. Available from: https://ajptonline.com/htmlpaper.aspx?journal=asian+journal+of+pharmacy+and+technology%3bpid%3d2014-4-1-2

24. Rajam RP, Muthukumar KR. An updated comprehensive review on nanosponges – novel emerging drug delivery system. Res J Pharm Technol. 2021; 14(8): 4476–84. Available from: https://rjptonline.org/abstractview.aspx?pid=2021-14-8-84

25. Sri KV, Santhoshini G, Sankar DR, Niharika K. Formulation and evaluation of rutin loaded nanosponges. Asian J Res Pharm Sci. 2018; 8(1): 21–4. : https://ajpsonline.com/abstractview.aspx?pid=2018-8-1-5

26. Anandam S, Selvamuthukumar S. Optimization of microwave-assisted synthesis of cyclodextrin nanosponges using response surface Methodology. 2014;

27. John D, Francis E, Yusuf FS. Research article development and evaluation of nanosponges loaded extended release tablets of lansoprazole. 2019;24–8.

28. Nitish, Jeganath S, Abdelmagid KFK. A review on nanosponges – a promising novel drug delivery system. Res J Pharm Technol 2021;14(1): 501–5. Available from: https://rjptonline.org/abstractview.aspx?pid=2021-14-1-91

29. Yadav GV, Panchory HP. “Nanosponges – a boon to the targeted drug delivery system.” J Drug Deliv Ther. 2013; 3(4):151–5.

30. Journals H, Article R. Nanosponges: a new approach for drug Targetting. 2016; 3.

31. Behura PR, Krishna V. A novel revolutionary approach of a synthesis and application of targeted nanosponge drug delivery. J Appl Pharm, 2021; 13(6): 297.

32. Krabicov I, Appleton SL, Tannous M, Hoti G, Caldera F, Pedrazzo AR, et al. History of cyclodextrin nanosponges. :1–23.

33. Ravi G, Bose PSC, Ravi V, Sarita D. Preparation, characterization and evaluation of celecoxib loaded nanosponges for the treatment of psoriatic arthritis. Int J Med Biomed Stud. 2019; 3(12): 181–5.

34. Shringirishi M, Mahor A, Gupta R, Prajapati SK, Bansal K, Kesharwani P. Fabrication and characterization of nifedipine loaded β-cyclodextrin nanosponges: an in vitro and in vivo evaluation. J Drug Deliv Sci Technol. 2017; 41:344–50. Available from: http://dx.doi.org/10.1016/j.jddst.2017.08.005

Received on 28.07.2023 Modified on 04.09.2023

Res. J. Pharma. Dosage Forms and Tech.2024; 16(1):67-75.

DOI: 10.52711/0975-4377.2024.00012

Name of the Drug	Route of administration	Brand Name	Dosage form
Iodine	Topical	Mena – Gargel	Solution
Alprostadil	Intravenous	Prostavastin	Injection
Dexamethasone	Dermal	Glymesason	Tablet
Piroxicam	Oral	Brevin	Capsule

Drug	Nano Sponge vehicle	Category of drug
Itraconazole	Beta-cyclodextrin	Antifungal
Voriconazole	Ethyl cellulose, polymethylmethacrylate [PMMA]	Antifungal
Miconazolenitrate	Beta-cyclodextrin, di-phenylcarbonate	Antifungal
Celecoxib	Beta-cyclodextrin, N, N-methylenebisacrylamide	NSAIDS
Erlotinib	Beta-cyclodextrin	Anticancer
Econazolenitrate	Ethylcellulose,PVA	Antifungal
Isoniazid	Ethylcellulose,PVA	Anti-tubercular
Cephalexin	Ethylcellulose,PVA	Antibiotic
Norfloxacin	Beta-cyclodextrin and diphenylcarbonate	Antibiotic
L-dopa	Beta-cyclodextrin	Parkinsondisease
Fenofibrate	Maizestarch,SDS	Fibrate
Nifedipine	Beta-cyclodextrin	Calciumchannelblocker
Glipizide	Beta-cyclodextrin	Sulfonylurea
Ibuprofen	Ethylcellulose,PVA	NSAIDS
Resveratrol	Cyclodextrin	Antioxidant
Paclitaxel	Beta-cyclodextrin	Antineoplastic
Campothecin	Beta-cyclodextrin	Antineoplastic
Tamoxifen	Beta-cyclodextrin	Antiestrogen
Temozolomide	Poly (valerolactinacallyvalcrolactone) and poly (valerolactinacallyvalcrolactoneoxepanedione)	Antitumor
Dexamethasone	Beta-cyclodextrin	Antitumor
Gamma-oryzanol	Beta-cyclodextrin	Antioxidant
Telmisartan	Carbonatedcrosslinkers	Antihypertensive
Lysozyme	Cyclodextrin basedpoly(amidoamine)	Enzyme
Nelfinavirmesylate	Beta-cyclodextrin	Antiviral