DEVELOPMENT OF NANOSPONGES-BASED TOPICAL FORMULATION FOR THE EFFECTIVE DELIVERY OF SELECTED ANTIFUNGAL DRUG

RUDROJU ANUSHA; MOTHILAL M.

doi:10.22159/ijap.2024v16i5.51466

Authors

RUDROJU ANUSHA Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, TamilNadu-603203, India
MOTHILAL M. Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, SRM Nagar, Kattankulathur, TamilNadu-603203, India https://orcid.org/0000-0003-0451-2890

DOI:

https://doi.org/10.22159/ijap.2024v16i5.51466

Keywords:

Luliconazole, Response surface methodology, Nanosponges, Freeze drying, Inclusion complex, Skin permeability

Abstract

Objective: To increase luliconazole's therapeutic impact, distribution, and preservation, this project is aimed to prepare cyclodextrin-based nanosponge gel and test its topical skin administration.

Methods: The convection heating method produced cyclodextrin-diphenylcarbonate nanosponges, which later loaded with luliconazole by freeze-drying. Response Surface Methodology (RSM) was used to examine the association between procedure parameters and quality variables. Pilot study findings were analyzed using Analysis of variance. Key technique factors affect quality metrics in contour, RSM, and perturbation graphs.

Results: The mean medication payload was 42.19±1.45 mg of luliconazole/g of lyophilized powder. The remarkable encapsulation efficiency of luliconazole (90.12±0.92%) supports an inclusion complex. Laser light scattering evaluation of luliconazole-loaded-nanosponges shows an unimodal and narrow particle size distribution of 60-73 nm. Drug encapsulation does not change a typical nanosponge's spherical form, according to microscopic investigations. Physico-chemical characterized verified the nanosponge-luliconazole inclusion complex. The complex release is faster than pure medication in vitro. Pure luliconazole dissolves 12% in 12 h, whereas nanosponge encapsulated medicine is absorbed faster and better. After 12 h, nanosponge formulations released 93-95% luliconazole. A model carbopol gel formulation with nanosponge formulations examined skin permeability, antifungal effectiveness, and stability. In 12 h skin permeation trials, nanosponge-encapsulated luliconazole leaked slowly across rat skin.

Conclusion: The slow drug release, greater skin penetration, and superior storage stability of the gel formulation based on cyclodextrin nanosponges of luliconazole imply that it has great potential as a topical delivery system.

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References

Khanna D, Bharti S. Luliconazole for the treatment of fungal infections: an evidence-based review. Core Evid. 2014 Sep;9:113-24. doi: 10.2147/CE.S49629, PMID 25285056.

Koga H, Nanjoh Y, Kaneda H, Yamaguchi H, Tsuboi R. Short-term therapy with luliconazole a novel topical antifungal imidazole in guinea pig models of tinea corporis and tinea pedis. Antimicrob Agents Chemother. 2012 Jun;56(6):3138-43. doi: 10.1128/AAC.05255-11, PMID 22391525.

Subair TK, Mohanan J. Development of nano-based film-forming gel for prolonged dermal delivery of luliconazole. Int J Pharm Pharm Sci. 2022 Feb;14(2):31-41. doi: 10.22159/ijpps.2022v14i2.43253.

Gunasheela S, Chandrakala V, Srinivasan S. Development and evaluation of microsponge gel of an antifungal drug. Int J Curr Pharm Res. 2023 Jan;15(1):30-41.

Maurya VK, Kachhwaha D, Bora A, Khatri PK, Rathore L. Determination of antifungal minimum inhibitory concentration and its clinical correlation among treatment failure cases of dermatophytosis. J Family Med Prim Care. 2019 Aug;8(8):2577-81. doi: 10.4103/jfmpc.jfmpc_483_19, PMID 31548935.

Dogra S, Shaw D, Rudramurthy SM. Antifungal drug susceptibility testing of dermatophytes: laboratory findings to clinical implications. Indian Dermatol Online J. 2019 Mar;10(3):225-33. doi: 10.4103/idoj.IDOJ_146_19, PMID 31149563.

Kumar M, Shanthi N, Mahato AK, Soni S, Rajnikanth PS. Preparation of luliconazole nanocrystals loaded hydrogel for improvement of dissolution and antifungal activity. Heliyon. 2019 May;5(5):e01688. doi: 10.1016/j.heliyon.2019.e01688, PMID 31193099.

Vivek D, Nishant B, Nikita G, Kajal T. Herbal ethosomal gel containing luliconazole for productive relevance in the field of biomedicine. Vol. 10(3). Biotech Publishing; 2020 Mar. p. 97.

Kaur M, Singh K, Jain SK. Luliconazole vesicular-based gel formulations for its enhanced topical delivery. J Liposome Res. 2020 Apr;30(4):388-406. doi: 10.1080/08982104.2019.1682602, PMID 31631734.

Lee BC, Pangeni R, Na J, Koo KT, Park JW. Preparation and in vivo evaluation of a highly skin and nail-permeable efinaconazole topical formulation for enhanced treatment of onychomycosis. Drug Deliv. 2019 Jan;26(1):1167-77. doi: 10.1080/10717544.2019.1687612, PMID 31738083.

Neofytos D, Avdic E, Magiorakos AP. Clinical safety and tolerability issues in use of triazole derivatives in management of fungal infections. Drug Healthc Patient Saf. 2010;2:27-38. doi: 10.2147/dhps.s6321, PMID 21701616.

Moskaluk AE, Vande Woude S. Current topics in dermatophyte classification and clinical diagnosis. Pathogens. 2022 Sep;11(9):957. doi: 10.3390/pathogens11090957, PMID 36145389.

Volkova TV, Simonova OR, Perlovich GL. New antifungal compound: impact of cosolvency micellization and complexation on solubility and permeability processes. Pharmaceutics. 2021 Nov;13(11):1865. doi: 10.3390/pharmaceutics13111865, PMID 34834280.

Tiwari G, Tiwari R, Rai AK. Cyclodextrins in delivery systems: applications. J Pharm Bioallied Sci. 2010 Feb;2(2):72-9. doi: 10.4103/0975-7406.67003, PMID 21814436.

Mamatha P, Bhikshapathi DV. Determination of in vitro cytotoxicity of entrectinib and pemigatinib nanosponges tablets on a 498, mcf-7, and panc-1 cell lines. Int J Pharm Pharm Sci. 2024 Feb;16(2):12-6. doi: 10.22159/ijpps.2024v16i2.49567.

Madhavi M, Shiva Kumar G. Preparation and evaluation of iguratimod oral formulation using cyclodextrin nanosponges. Int J Appl Pharm. 2022 May;14(5):78-87. doi: 10.22159/ijap.2022v14i5.45044.

Bhagyavathi A, Sai Lakshmi TK, Sahitya DM, Bhavani B. Nanosponges-a revolutionary targeted drug delivery nanocarrier: a review. Asian J Pharm Clin Res. 2023 Apr;16(4):3-9. doi: 10.22159/ajpcr.2023v16i4.46453.

Darandale SS, Vavia PR. Cyclodextrin based nanosponges of curcumin: formulation and physicochemical characterization. J Incl Phenom Macrocycl Chem. 2013 Apr;75(3-4):315-22. doi: 10.1007/s10847-012-0186-9.

Rajewski J, Dobrzynska Inger A. Application of response surface methodology (RSM) for the optimization of chromium(III) synergistic extraction by supported liquid membrane. Membranes (Basel). 2021 Nov;11(11):854. doi: 10.3390/membranes11110854, PMID 34832083.

Anandam S, Selvamuthukumar S. Fabrication of cyclodextrin nanosponges for quercetin delivery: physicochemical characterization photostability and antioxidant effects. J Mater Sci. 2014 Dec;49(23):8140-53. doi: 10.1007/s10853-014-8523-6.

Swaminathan S, Vavia PR, Trotta F, Cavalli R, Tumbiolo S, Bertinetti L. Structural evidence of differential forms of nanosponges of beta-cyclodextrin and its effect on solubilization of a model drug. J Incl Phenom Macrocycl Chem. 2013 Feb;76(1-2):201-11. doi: 10.1007/s10847-012-0192-y.

Nazzal S, Khan MA. Response surface methodology for the optimization of ubiquinone self-nanoemulsified drug delivery system. AAPS PharmSciTech. 2002;3(1):E3. doi: 10.1208/pt030103, PMID 12916956.

Anandam S, Selvamuthukumar S. Optimization of microwave assisted synthesis of cyclodextrin nanosponges using response surface methodology. J Porous Mater. 2014 Jun;21(6):1015-23. doi: 10.1007/s10934-014-9851-2.

Shivakumar HN, Patel PB, Desai BG, Ashok P, Arulmozhi S. Design and statistical optimization of glipizide loaded lipospheres using response surface methodology. Acta Pharm. 2007 Sep;57(3):269-85. doi: 10.2478/v10007-007-0022-8, PMID 17878108.

Pimple S, Manjappa AS, Ukawala M, Murthy RS. PLGA nanoparticles loaded with etoposide and quercetin dihydrate individually: in vitro cell line study to ensure advantage of combination therapy. Cancer Nano. 2012;3(1-6):25-36. doi: 10.1007/s12645-012-0027-y.

Verma P, Pathak K. Nanosized ethanolic vesicles loaded with econazole nitrate for the treatment of deep fungal infections through topical gel formulation. Nanomedicine. 2012 Apr;8(4):489-96. doi: 10.1016/j.nano.2011.07.004, PMID 21839053.

Song CK, Balakrishnan P, Shim CK, Chung SJ, Chong S, Kim DD. A novel vesicular carrier transethosome for enhanced skin delivery of voriconazole: characterization and in vitro/in vivo evaluation. Colloids Surf B Biointerfaces. 2012 Apr;92:299-304. doi: 10.1016/j.colsurfb.2011.12.004, PMID 22205066.

Vicentini FT, Simi TR, Del Ciampo JO, Wolga NO, Pitol DL, Iyomasa MM. Quercetin in w/o microemulsion: in vitro and in vivo skin penetration and efficacy against UVB-induced skin damages evaluated in vivo. Eur J Pharm Biopharm. 2008 Mar;69(3):948-57. doi: 10.1016/j.ejpb.2008.01.012, PMID 18304790.

Puglia C, Blasi P, Rizza L, Schoubben A, Bonina F, Rossi C. Lipid nanoparticles for prolonged topical delivery: an in vitro and in vivo investigation. Int J Pharm. 2008 Feb;357(1-2):295-304. doi: 10.1016/j.ijpharm.2008.01.045, PMID 18343059.

Bauer AW, Kirby WM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966 Apr;45(4):493-6. doi: 10.1093/ajcp/45.4_ts.493, PMID 5325707.

Chilajwar SV, Pednekar PP, Jadhav KR, Gupta GJ, Kadam VJ. Cyclodextrin based nanosponges: a propitious platform for enhancing drug delivery. Expert Opin Drug Deliv. 2014 Jan;11(1):111-20. doi: 10.1517/17425247.2014.865013, PMID 24298891.

Swaminathan S, Cavalli R, Trotta F, Ferruti P, Ranucci E, Gerges I. In vitro release modulation and conformational stabilization of a model protein using swellable polyamidoamine nanosponges of β-cyclodextrin. J Incl Phenom Macrocycl Chem. 2010 Mar;68(1-2) :183-91. doi: 10.1007/s10847-010-9765-9.