Nano Sponges: A Potential Drug Delivery Approach

 

Janani Sadhasivam, Abimanyu Sugumaran*, Damodharan Narayanaswamy

Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur 603203, India.

 

ABSTRACT:

Recently, the progress in nanotechnology has led to the advancement of the delivery of drugs to the targeted site (TDDS). The introduction of Nano sponges has been an important step in conquering certain complications like toxicity of drug, its poor bioavailability, and release of medicament in a predictable manner. Currently, Nano sponges have achieved excellent impacts in delivering drugs through nanotechnology in which the nanosponges are porous in nature with tiny sponges (below 1 μm), circulating throughout the body. Therefore, they reach the target site and stick to the skin surface and release the drug in a controlled manner. A large variety of drugs can be encapsulated into the cavity of Nano sponges and it carries both hydrophilic and lipophilic drugs. Nano sponges (NSs) drug delivery system has been considered as one the most assuring field in pharmacy. It can be utilized as carrier for biocatalyst in the release of enzymes, vaccines, antibodies, and proteins. The current review focuses on the preparation method, evaluation and potential use in drug delivery system.

 

 

 

INTRODUCTION:

The term nanotechnology was first introduced by Richard Feynman in the year 1959.¹ It is defined as controlling, noticing, and treating different human body systems at the sub-atomic level utilizing both nano-devices as well as nanostructures. Nanotechnology is one of the most well-known areas of logical research, particularly for medical applications.² It is one of the new patterns in the delivery of medication systems in the pharmacy and biomedical fields.³ Delivery of drugs has numerous impacts on medical innovation, extraordinarily improving the exhibitions of much-existing medication and empowering, utilizing altogether for new treatments.⁴ Drugs to be delivered at the target site has long been a problem for medical analyst i.e., how to deliver them at a target site in the body and how to limit the drug release to avoid overdoses.

 

The term Nanosponges (small sponges with porous structure) are found to be a new and complex molecule which have potent effect on the above- mentioned problems.⁵ Hence it has been recently introduced and advanced for drug delivery.⁶ Previously, Nanosponge drug delivery (NSDD) system was only used as a topical delivery system, but currently it can be carried out by both oral and intravenous (IV) route.⁷ Nanosponges plays a vital role in controlling the rate of drug delivery at the target site due to its small size and effective carrier characteristics such as molecular weight ranging between 100 to 400 dalton, melting point(<250⁰C). Nanosponges are substances that are made up of microscopic particles with wide cavities having less nanometer, in which enormous varieties of materials can be encapsulated. Nanosponges have the ability to carry both hydrophilic as well as lipophilic substances.⁸ and their bioavailability by altering the pharmacokinetic parameters of drug molecules.⁹ Nanosponges degrade naturally due to its 3-dimensional scaffold or polyester nature. Nanosponges are formed by mixing both polyester and cross-linker in a solution. Due to biodegradable nature of polyester, it sufficiently breaks down in the body. The drug-loaded in the nanosponges releases when the scaffold of nanosponges breaks down.¹⁰ Nanosponges are advantageous for the medication of several complications and it is more efficient for breast cancer than the conventional method.^11,12 Nanosponges deliver the drug at the tumor site rather than distributed throughout the body. Hence, it is highly sufficient for a given dose and has fewer adverse effects because of lesser amount of drug comes into contact with normal tissues.¹³ Nanosponges are durable at temperature about 300°C and they have less than 1 μm in diameter.

 

Figure 1: Schematic representation of Structure of a nanosponge with drug loading cavity.

 

Table1: Different Chemicals used for the preparation of Nanosponge:

POLYMERS	COPOLYMERS	CROSS- LINKERS	APROTIC SOLVENTS
Hyper cross-linked polystyrenes	Ethylcellulose	Diphenyl carbonate	Methanol
Cyclodextrins and its derivatives like Methyl β- Cyclodextrin. Alkyloxycarbonyl Cyclodextrins, 2-Hydroxy Propyl β-Cyclodextrins	Polyvinyl alcohol		ethanol
	Hydroxypropyl methylcellulose (HPMC)	Diaryl carbonate	dimethylformamide
	Poly (Valero lactone-allyl Valero lactone),	Acetic acid	dimethyl sulphoxide
	Poly (valerolactone-allylvalerolactone oxepanedione).	Dichloromethane	dimethylacetamide
		Epichloridine Glutaraldehyde
		Carboxylic acid dianhydrides

 

TYPES OF NANOSPONGES:

 

ADVANTAGES:

Nanosponges will enhance the aqueous solubility of drugs which are poorly water-soluble and release the molecules of a drug in a predictable manner. They are used to eliminate the poisonous substances from the body, reduces the adverse effects and thereby decrease the dosing frequency. Nanosponges will enhance the stability of formulation and also increase its flexibility. They are non-toxic, non-irritating, non-mutagenic and have better patient compliance. Bacteria cannot penetrate the nanosponges, due to pore size which is tiny and behaves like self-sterilizer.^14,15,16

 

Nanosponges gives a predetermined release of drug and it is site-specific drug delivery system and the preparations are used to mask the unpleasant tastes of drugs. Liquid substance gets converted to solids by using nanosponges and the particles can be formulated accordingly i.e. small or large by changing the cross-linked proportion to the polymer. They also improve dissolution.^{17, 18,19,20,21}

 

DISADVANTAGES:

Nanosponges are not suitable for large molecules, sometimes dumping of doses may take place.²² They have the ability to encapsulate the smaller molecules. Drug loading capacity gets damaged by the degree of crystallinity.^23,24 Only smaller molecules can be prepared by nanosponges and depend on loading capacities.^25,18

 

MECHANISM OF DRUG RELEASE FROM NANOSPONGES:

Due to the open structure of nanosponges, active substances are added in an encapsulated form to the vehicle which has the ability to move easily from the particle into the vehicle. Equilibrium is obtained and the vehicle gets saturated. The vehicle consisting of active pharmaceutical ingredients is not saturated and thereby causes disturbance to the equilibrium when the drug is applied to the skin. The vehicle gets either dried or absorbed when the flow of active principles from nanosponge particles into vehicles starts to epidermis. The release of active ingredient stays on skin for a prolonged time even after the retention of nanoparticles on the skin surface.¹⁰

 

LOADING OF NANOSPONGES:

The Nanosponges should be pre-treated in order to acquire particle size (<500 nm). To prevent the presence of aggregates the nanosponges were suspended in water and sonicated and hence to obtain colloidal fraction it is centrifuged. The supernatant was isolated and by the method of freeze-drying, the sample is dried.²⁶ The aqueous suspension of nanosponges was prepared and surplus quantity of the drug was diffused and the suspension was kept under continuous stirring for the particular time needed for complexation. After complexation, by using the method of centrifugation the uncomplexed (undissolved) drug was isolated from the complex drug. By solvent evaporation method the solid crystals of nanosponges were attained.^26,27 The nanosponges’ crystal structure plays a vital role in complexation with drug. In crystalline nanosponges the capacity of drug loading is higher when compared to paracrystalline nanosponges. If the nanosponges are poorly crystalline in nature, the drug infusion occurs as a mechanical mixture instead of inclusion complex.²⁷

 

METHOD OF PREPARATION:

SOLVENT METHOD:

In solvent method, the Nano sponges are formulated by mixing the polymer with polar aprotic solvents i.e. Dimethylformamide [DMF] and Dimethyl sulfoxide [DMSO]. To this mixture, a crosslinker is added to a 1:4 ratio. Mostly used cross-linkers are carbonyl compounds i.e. Carbonyldiimidazole and Dimethyl carbonate and the reaction should take place at 10℃ of temperature, to reflux the temperature of the solvent for 1 to 48 h.¹² The solution is cooled down after the reaction is completed and then the product obtained is added to bi-distilled water, by draining the product and refining it by using Soxhlet extraction with ethanol and further drying, the product is recovered. To obtain homogenous powder, the product is dried under vacuum and using mechanical mill it is ground.¹⁵

 

 

Figure2: Schematic Representation of Preparation of Nanosponges by Solvent Method.

 

ULTRA-SOUND ASSISTED SYNTHESIS

In Ultra-sound assisted synthesis the nanosponges are uniform and spherical in size.⁸ Without using the solvent, the polymers are allowed to react with the crosslinkers in a flask which is then placed in an ultrasound bath filled with water which is made to heat up to 90⁰C. The mixture is sonicated for 5h and cooled down to room temperature which is then crushed into rough pieces. With the use of the Soxhlet apparatus (ethanol) and by washing the product with water the non-reacting polymer is removed and nanosponges are obtained.²⁸ Diphenyl carbonate or pyromellitic anhydride is the cross-linkers used in this method.^29,30

 

Figure 3: Schematic Representation of Preparation of Nanosponges by Ultra-Sound Assisted Synthesis

 

EMULSION SOLVENT DIFFUSION METHOD:

In Emulsion solvent diffusion technique, various concentrations of polyvinyl alcohol and ethyl cellulose are used to formulate nanosponges. Continuous and dispersed are the two phases used in this method. Drug and ethyl cellulose is dissolved in dichloromethane which comprises of the dispersed phase and then gradually added to aqueous phase which consists of Polyvinylalcohol. The crosslinker is then added to it by stirring for 2-4h at 2000 rpm then the nanosponges are filtered followed by drying in hot air oven at 40°C for 24 hours.³¹ To remove the residual solvent dried nanosponges are kept in vacuum desiccator.

 

 

CHARACTERIZATION OF NANOSPONGES:

1.     Solubility Studies:

The widely used technique to study inclusion complexes is the phase solubility method by which the effectiveness of nanosponges on the solubility of drugs which shows the degree of complexation is explained as well as the bioavailability of the drug is determined.³²

 

2.     Microscopy Studies:

 Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM) is used for the visualization of the nanosponges, drug, and (complex of drug/nanosponge). When viewed under an electron microscope, inclusion complexes are formed which indicates the variation in crystallization state of the product and the crude material.^33,34

 

3.     Particle Size And Polydispersity:

The drug’s particle size can influence the solubility of the drug and its release. Particle size distribution is determined by the technique of dynamic light scattering (DLS) by which, a software named 90Plus is used for determining particle size. From which, the poly-dispersity index (PDI) and the mean diameter of the particles can be identified.

 

4.     Zeta Potential:

By using zeta sizer, zeta potential can be measured by which the surface charge of Nansponges could be determined. If the value of zeta potential is greater than 30mV it indicates that the formulation is well stable.³⁵

 

5.     Thin Layer Chromatography

In thin-layer chromatography (TLC), the Retention factor (Rf value) of a drug substance decrease to a considerable range in which it helps in determining the formation of complex between the Nanosponges (NSs) and the drug.³⁶

 

6.     Drug Loading Efficiency

The drug loading capacity of Nanosponges can be determined by the quantitative estimation of drug-infused into nanosponges by using the method of high-performance liquid chromatography (HPLC) and Ultraviolet spectrophotometer.³⁷ In this, the quantity of drug-infused into the nanosponges is weighed and diffused in an appropriate solvent and then it is sonicated for a particular time period, furthermore, it is diluted, and measured by UV spectrophotometer or HPLC technique.³⁸

 

The percentage of loading efficiency of NSs can be estimated by using the equation.³⁹

 

                                          Actual drug content

Loading efficiency = ----------------------------------× 100

Theoretical drug content

 

7.     Infrared Spectroscopy:

The interaction between the drug as well as the nanosponges (solid-state) can be analyzed by using spectroscopy. When the complexes are formed the Nanosponge bands are slightly altered. In the nanosponge complexes few guest molecules are attached (<25%) the spectrum of the drug could be easily masked by the nanosponge spectrum.⁴⁰ This method is not suitable to find the inclusion complexes.³⁴ The application of the infra-red spectroscopy is restricted to drugs owing some of the characteristic bands, namely carbonyl group or sulfonyl group.

 

TOXICITY STUDIES:

Toxicity study is essential to measure drug safety profiles and optimizing efficient doses for their effective application in both animals and in humans.

 

ACUTE TOXICOLOGICAL STUDY:

No death was identified in male Wistar rodents, after 28 days of oral administration, of nanosponges dose ranging from 300 to 2000 mg/kg. Furthermore, there were no differences in general appearance. In comparison to the control groups, the animals treated did not show any signs of diarrhea, tremors, convulsions, etc. Thus it indicates that β-cyclodextrin nanosponge is extremely safe and non-toxic when given orally at a dose (> 2000 mg/kg body weight).⁴¹

 

REPEATED TOXICOLOGICAL STUDY:

After 28 days of oral administration of nanosponges, it does not show any significant difference in body weight and hematological parameters like RBC, WBC, and hemoglobin were observed. In addition, there was no indication of liver damage, renal toxicity, and hepatic toxicity because of the enzymes like aspartate, aminotransferase, urea, creatinine, alanine aminotransferase remain unaffected. Thus hyper cross-linked β-cyclodextrin polymers are biocompatible and do not degrades during the time of transit via gastrointestinal tract (GIT).⁴¹

 

MTT test says that the nanosponges are not toxic in in vitro studies on various cell lines [namely HCPC-I, MCF7, HELA, COS]. Furthermore, nanosponges at 15 mg/mL concentration do not show hemolytic activity after incubating it for 90 min with human erythrocytes and also compatibly good with blood. Synthesis of nanosponges from PMDA shows good stability in acidic solutions and is less stable in basic.

 

 

Table 2: List of some Marketed Formulations of Nanosponges:

Drug name	Trade name	Composition	Route of administration	Dosage form	Indications
Iodine	Mena-gargle	Iodine and β cyclodextrin	Topical route	Solution	As disinfectant for throat infection
Alprostadil	Prostavastin	Prostaglandin E1 and αcyclodextrin	I.V route	Injection	Chronic atterial occlusive disease, hypotension is controlled
Piroxicam	Brexin	Piroxicam and β-cyclodextrin	Oral route	Capsule	As Analgesic
Dexamethasone	Glymesason	Dexamethasone and βcyclodextrin	Dermal route	Tablet	Analgesic

 

APPLICATIONS:

1.     Nanosponges for Drug Delivery:

Due to the tiny porous structure of nanosponges, it can able to carry water-insoluble drugs.¹⁰ The Nanosponges complex plays a major role in enhancing the dissolution rate, permeability, and solubility of a drug. When compared to direct injection, B cyclodextrin based nanosponges will deliver the drug three to five times more to the target site.¹¹ Drugs which have solubility problem could be delivered successfully by infusing them into the nanosponges. They are solid in nature and prepared for topical, oral, parental dosage forms. For formulating tablets or capsules the complexes are diffused in a matrix of diluents, excipients, anti-caking agents, lubricants for oral administration.¹² In the case of the parenteral route of administration the complexes are carried out in saline, sterile water or other liquid solutions.¹² and for topical administration they are carried through topical hydrogels.^42,43

 

2.     Nanosponges for Protein Delivery:

By encapsulating or adsorbing them in cyclodextrin nanosponges, proteins can be carried.⁴⁴ Due to the instability of protein solution of bovine serum albumin, they are stored in lyophilized form and they can get changed to denatured form on lyophilization. The main disadvantage in preparation and development of protein is maintaining its native structure and storing it for a long period during and after processing. Nanosponges will enhance the stability of proteins and used for enzyme immobilization, stabilization, protein encapsulation, and subsequent controlled delivery.²²

 

3.     As Absorbent in Treating Poison in Blood:

Nanosponges are used to remove poisonous substances which is dangerous from the blood by absorbing the poison. Nanosponges can soak up the toxins when administered through injection and they are better when compared to antidotes. Nanosponges looks like a red blood cell in a bloodstream they trick the toxins into attacking and absorbs them. Nanosponges can absorb the toxin molecules depending on the toxin.⁴⁵ For example β-Cyclodextrin complexed polyurethane polymer nanosponge is utilized to remove the ochratoxin A levels from red wine and aqueous solutions. The nanosponges are capable of adsorbing 0.22mg ochratoxin A per mg of polymer.⁴⁶

4.     Antiviral Application:

For selective delivery of small interfering RNA or antiviral drugs to the lungs and nasal epithelia nanosponges are good carrier and also target viruses which affect the Respiratory Tract Infections such as rhinovirus, influenza virus, and further targets Hepatitis B virus (HBV), Human Immunodeficiency Virus (HIV) as well as Herpes simplex virus(HSV). E.g. The capacity of infused drug Acyclovir in carboxylated nanosponges was resulted to be 60% w/w. Furthermore, by performing an invitro profile, the release of drug was in a sustained manner when compared to pure drugs it showed greater antiviral efficiency against HSV.^47,48 Drugs that are used are saquinavir, zidovudine, acyclovir.^49,7

 

5.     Role of Nanosponges for the Treatment of Fungal Infections:

One of the most dreaded diseases around the world is fungal infection.⁵⁰ To treat these coetaneous infections topical treatment is an effective choice because of its various advantages like targeting of medicaments to the particular site of disease and decreases its adverse effects. An effective antifungal or fungicide that is used topically to cure various skin diseases like vaginal thrush, tinea pityriasis Versicolor, ringworm, jock itch, and athlete’s foot is econazole nitrate which is available in the form of cream, ointments, lotions, and solutions. Econazole nitrate is only effective when it is combined with a high concentration of active substances and then applied to the skin. Serving this purpose, with the usage of emulsion solvent method econazole nitrate nanosponges were fabricated and then infused in a hydrogel to release the drug in a sustained manner as topical application.^51,52

 

6.     Topical Delivery Systems:

For the controlled release of topical agents, nanosponge delivery is a unique technology.²² they maintain efficacy by reducing skin irritation. Antibiotics, antifungals, local anesthetics (LA) are the category of drugs that are prepared as topical nanosponges. These nanosponges encapsulate and suspend in broad category of substances and then made into final products namely cream, capsules, liquid, and tablet.⁵³ Drugs that are prepared as antifungal nanosponges are miconazole nitrate, itraconazole nitrate, ketoconazole, and voriconazole.^47,19

CONCLUSION:

Nanosponges (NSs) are nano-sized particles with porous nature in which they can easily penetrate through the skin surface. These particles have the ability to carry both lipophilic as well as hydrophilic drug substances in which they can efficiently deliver the drug substance in a controlled manner at a particular site so it is site-specific drug delivery system. Therefore, nanosponges offers advantageous effects such as increases the safety, enhances stability, decreases the side effects, bioavailability is increased and patient compliance is also improved. Due to its small size and efficient characteristics, it can deliver drugs by numerous routes of administration like oral in the form of (tablets, capsules), topical (eg. Creams, ointments, gels) and parenteral route in a controlled manner to the site of target. In addition to their importance in the field of drug delivery, there are some promising applications remain for agrochemistry, bioremediation processes, cosmetics, biomedicine, and catalysis. The Drugs that are delivered by nanosponges are proved to be safer and effective and therefore, the pharmaceutical industries will be highly benefited if clinical studies can prove their potential for human use.

 

ACKNOWLEDGEMENT:

The authors are grateful to the Dean and faculties of SRM college of pharmacy SRMIST Kattankulathur for the facilities.

 

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

 

REFERENCE:

1.      James R. Baker, Quintana A, Piehler L, Banazak-Holl M, Tomalia D , R E. The Synthesis and testing of anticancer therapeutic nanodevices. Biomedical micro devices. 2001; 3(1): 61- 69.

2.      Kalyankar T. M., Butle S. R., Chamwad G. N. Application of Nanotechnology in Cancer Treatment. Research Journal of Pharmacy and Technology. 2012;5(9): 1161-1167.

3.      Birajdar G.O, V.S. Kadam V.S, Chintale A.G, Halle P.D, Nabde M.K, Maske K.S. A Comprehensive Review on Nanotechnology. Research Journal of Pharmacy and Technology.2013; 6(5): 486-495.

4.      Cheng Y, Morshed RA, Auffinger B, Tobias AL and Lesniak MS. Multifunctional nanoparticles for brain tumor imaging and therapy. Advanced Drug Delivery Reviews. 2014; 66: 42-57.

5.      Subramanian S, Singireddy A, Krishnamoorthy K, Rajappan M. Nanosponges: A Novel drug delivery system-Review. Journal of Pharmacy and Pharmaceutical Sciences. 2012; 15(1): 103 -111.

6.      Shringirishi M, Prajapati S.K, Mahor A, Alok S , Yadav P, Verma A. Nanosponges: a potential nanocarrier for novel drug delivery-a review. Asian Pacific Journal of Tropical Disease. 2014; 4(Suppl 2): 519-526.

7.      Yadav G, Panchory HP. Nanosponges–a boon to the targeted drug delivery system. Journal of Drug Delivery & Therapeutics. 2013; 3(4): 151-5.

8.      Trotta F, Cavalli R, Tumiatti W, Zerbinati O, Rogero C, Vallero R. Ultrasound-assisted synthesis of Cyclodextrin-based nanosponges.2007; Euroean Patent 1 786 841 B1.

9.      Bezawada S, Charanjitha, Reddy V.M, Naveena, Gupta V.R. Nanosponges- A Concise Review For Emerging Trends. International Journal of Pharmaceutical Research and Biomedical Analysis. 2014; 3(1): 1-6.

10.   Bhowmik H, Venkatesh DN, Kuila A, Kumar KH. Nanosponges: A Review. International Journal of Applied Pharmaceutics. 2018;10(4):1-5.

11.   David F. Nanosponge drug delivery system more effective than direct injection. 2010; from https://phys.org/news/2010-06-nanosponge-drug-delivery-effective.html.

12.   Jenny A, Merima P, Alberto F, Francesco T. Roleof β- cyclodextrin nanosponges in polypropylene photooxidation. Carbohydrate Polymers, 2011; 86(1):127– 135.

13.   Subramanian S. Multifunctional Nanosponges for the Treatment of Cancer- A Review. Journal of Pharmaceutical Sciences & Research. 2017;9(12):2661-2668.

14.   Thakre AR, Gholse YN, Kasliwal RH. Nanosponges: a novel approach of drug delivery system. Journal of Medical Pharmaceutical and Allied Sciences. 2016;78:103-11.

15.   Lala R, Thorat A, Gargote C. Current trends in β- cyclodextrin based drug delivery systems. International Journal of Research Ayurveda and Pharmacy, 2011; 2(5): 1520-1526.

16.   Ahmed RZ, Patil G, Zaheer Z. Nanosponges–a completely new nano-horizon: pharmaceutical applications and recent advances. Drug Development and Industrial Pharmacy. 2013; 39(9): 1263-72.

17.   Jilsha G, Viswanand V. Nanosponge A Novel Approach of Drug Delivery System. International Journal of pharmaceutical Science Review And Research 2013; 19(2): 119-123.

18.   Balasaheb M. T, Patil P. M, Jahagirdar A. C, Khandekar D. B. Nanosponge An Emerging Drug Delivery System. International Journal of Institutional Pharmacy and Life sciences.2015;5(6).

19.   Vishwakarma A, Nikam P, Mogal R, Talale S. Nanosponges: A Benifiaction for Novel drug Delivery system. International Journal of Pharm. Tech Sciences.2014; 6(1):11-20.

20.   Patel E. K, Oswal R. J. Nanosponge and Micro Sponges: A Novel Drug Delivery System. International Journal of Research In Pharmacy And Chemistry. 2012; 2(2): 237-244.

21.   Nilesh J, Ruchi J, Navneet T, Braham Prakash G, Deepak Kumar J. Nanotechnology: A Safe and Effective Drug Delivery Systems. Asian Journal of Pharmaceutical and Clinical Research. 2010; 3(3):159-165.

22.   Singh D, Soni GC, Prajapati SK. Recent advances in nanosponges as drug delivery system: a review. Euroean Journal of Pharmaceutical and Medical Research 2016;3(10):364-71.

23.   Rahi, N.; Kumar, K. 2017. Nanosponges: A new era of versatile drug delivery system. Univ. J. Pharm. Res., 2(3), 31-5. DOI: 10.22270/ujpr.v2i3.RW4

24.   Dubey, P.; Sharma, H.K.; Shah, S.; Tyagi, C.K.; Chandekar, A.K.; Jadon, R.S. 2017.Formulations and evaluation of cyclodextrin complexed cefadroxil-loaded nanosponges. Int. J. Drug Del., 9(3), 84-100. DOI: 10.5138/09750215.2180

25.   Kundlas J, Nautiyal ., Jassal M. Nanosponges: As Originated Form For Targeted Drug Delivery. International Journal of Recent Advances In Pharmaceutical Research. 2015; 5(2): 75-81.

26.   Setijadi E, Tao L, Liu J, Jia Z, Boyer C, Davis TP. Biodegradable star polymers functionalized with betacyclodextrin inclusion complexes. Biomacromolecules. 2009; 10(9):2699-707.

27.   Cavalli R, Rogero CM, Mognetti B, Berta GN, Tumiatti V, Trotta F. Cyclodextrin-based nanosponges as a vehicle for antitumoral drugs. WO 2009/003656 A1. 2009.

28.   Arshad Ahmed Khan K. Nanosponges: A New Approach for Drug Targetting. International Journal of Pharmacy and Pharmaceutical Research. 2016; 7(3): 381-96.

29.   Patil T.S, Nalawade N.A, Kakade V.K, Kale S.N. Nanosponges: A novel targeted drug delivery for cancer treatment. International Journal of Advance Research and Development. 2017; 2(4): 55-62.

30.   Osmani R.A, Thirumaleshwar S, Bhosale R.R, Kulkarni P.K. Nanosponges: The spanking accession in drug delivery- An updated comprehensive review. Der. Pharmacia Sinica. 2014; 5(6): 7-21.

31.   Sharma R, Pathak K. Nanosponges: Emerging drug delivery system. Pharma Stud. 2010; 33-5.

32.   Sharma R, Roderick B, and Pathak K. Evaluation of kinetics and mechanism of drug release from Econazole nitrate Nanosponges loaded carbopol Hydrogel. Indian Journal of Pharmaceutical Education and research. 2011; 45(1):25-31.

33.   Shankar S, Linda P, Loredana S, Francesco T, Pradeep V, Dino A, Michele T, Gianpaolo Z, Roberta C. Cyclodextrin-based nanosponges encapsulating camptothecin: Physicochemical characterization, stability and cytotoxicity. Euroean Journal of Pharmaceutics and Biopharmaceutics. 2010; 74(2): 193-201.

34.   Ramnik S, Nitin B, Jyotsana M, Horemat SN. Characterization of Cyclodextrin Inclusion complexes –A Review. Journal of Pharmaceutical Science and Technology. 2010; 2(3):171-183.

35.   Rosalba M, Roberta C, Roberto F, Chiara D, Piergiorgio P, Leigh E, Li S, Roberto P. Antitumor activity of nanosponge-encapsulated Camptotechin in human prostate tumors. Cancer Research. 2011; 71(8):4431.

36.   Moura FC, Lago RM. Catalytic growth of carbon nanotubes and nanofibers on vermiculite to produce floatable hydrophobic “nanosponges” for oil spill remediation. Applied Catalysis B. 2009; 90(3-4): 436-40.

37.   Singh R, Bharti N, Madan J, Hiremath SN. Characterization of cyclodextrin inclusion complexes-a review. Journal of Pharmaceutical Science and Technology. 2010; 2(3) :171-83.

38.   Emanuele A, Dinarvand R. Preparation, Characterization and Drug Release from Thermoresponsive Microspheres. International Journal of Pharmaceutics.1995; 118(2) : 237-42.

39.   Boscolo B, Trotta F, Ghibaudi E. High catalytic performances of Pseudomonas fluorescens lipase adsorbed on a new type of cyclodextrin-based nanosponges. Journal of Molecular Catalysis B: Enzymatic. 2010; 62(2):155-61.

40.   Farooq SA, Saini V. Application of novel drug delivery system in the pharmacotherapy of hyperlipidemia. Journal of Chemistry and Pharmaceutical Sciences.2013; 6(3):138-46.

41.   Shende P, Kulkarni Y.A, Gaud R.S, Cavalli R, Ttrotta F, Deshmukh K, Caldera F. Acute and repeated dose toxicity studies of different β-cyclodextrin-based nanosponge formulation. Journal of Pharmaceutical Sciences. 2015; 104(5): 1856–63.

42.   Renuka S, Roderick BW, Kamla P. Evaluation of the kinetics and mechanism of drug release from Econazole Nitrate nanosponge loaded carbapol hydrogel. Indian Journal of Pharmaceutical Education and Research. 2011; 45(1): 2531.

43.   Renuka S, Kamla P. Polymeric nanosponges as an alternative carrier for improved retention of econazole nitrate onto the skin through topical hydrogel formulation. Pharmaceutical Development and Technology. 2011; 16(4):367-376.

44.   Gilardi G, Trota F, Cavalli R, Ferruti P, Ranucci E, Di Nardo G, Roggero C, Tumiatti V. Cyclodextrin nanosponges as carrier for biocatalysts, and in the delivery and release of enzymes, proteins, vaccines and antibodies. WO2009149883 A1; 2009.

45.   Che-Ming J Hu, Ronnie H Fang, Jonathan Copp, Brian T Luk, Liangfang Zhang. A biomimetic nanosponge that absorbs pore forming toxins. Nature Nanotechnology. 2013; 8:336–40.

46.   Appell M, Jackson M.A. Sorption of Ochratoxin A from aqueous solutions using β cyclodextrin-polyurethane polymer. Toxins. 2012; 4(2), 98-109.

47.   Shivani S, Poladi K.K. Nanosponges -A novel emerging drug delivery system: A review. International Journal of Pharmaceutical Science and Research .2015; 6(2), 529-40.

48.   Trotta F, Zanetti M, Cavalli R. Cyclodextrin-based nanosponges as drug carriers. Beilstein Journal of Organic Chemistry. 2012; 8, 2091-9.

49.   Ansari K.A, Torne S, Vavia P.R, Trotta F, Cavalli R. Cyclodextrin - Based Nanosponges for Delivery of Resveratrol: In Vitro Characterization, Stability, Cytotoxicity and Permeation Study. AAPS Pharm Sci Tech. 2011; 12, (1): 279-86.

50.   Trotta F. Cyclodextrin Nano sponges and their applications. Cyclodextrins in pharmaceutics, cosmetics, and biomedicine. Current and Future Industrial Applications. 2011; 323-42.

51.   Kaur G, Aggarwal G, Harikumar SL. Nanosponge: New colloidal drug delivery system for topical delivery. Indo Global Journal of Pharmaceutical Sciences. 2015; 5(1):53-7.

52.   Kadian R. Nanoparticles: a promising drug delivery approach. Asian Journal of Pharmaceutical and Clinical Research. 2018;11(1):30-5.

53.   Pawar S, Shende P, Trotta F. Diversity of β-cyclodextrin-based nanosponges for transformation of actives. International Journal of Pharmaceutics. 2019; 565(1):333-350.

 

 

Received on 28.10.2019           Modified on 16.12.2019

Accepted on 19.01.2020         © RJPT All right reserved