Effect of fluconazole and terbinafine nanoparticles on the treatment of dermatophytosis induced by Trichophyton mentagrophytes in guinea pig
Background and Objectives: Dermatophytosis induced by Trichophyton mentagrophytes is a major human and animal fungal contamination. Antifungals like terbinafine and fluconazole are widely used to treat dermatophytosis; nevertheless, the prevalence of drug resistance has increased. Hence, novel curative strategies are needed. In the present study, we compared the efficacies of conventional and nanoform of antifungals agents in guinea pig model of dermatophytosis.
Materials and Methods: Guinea pigs (n=36) were injected (the posterior dorsal portion) with Trichophyton mentagrophytes conidia. The guinea pigs were divided into 6 groups (positive control, negative control, fluconazole 0.5% treated group, nano-fluconazole treated group, terbinafine 1% treated group, and nano-terbinafine treated group), then were scored both clinically (redness and lesion intensity) and mycologically (microscopy and culture) until day 40 of inoculation. The treatment started 5 days after the inoculation and continued until day 40 of inoculation.
Results: Assessment of the mean score of clinical lesions in groups treated with nano-drug forms of fluconazole and terbinafine on the first day of treatment showed a score of 3 (significant redness with large scaling) and for the conventional form of terbinafine and fluconazole had a score of 4 (ulcer and scar). The decrease in lesion score in nano-drug treated groups was observed between days 15 and 20 and continued until day 40. On day 40, all groups had zero scores except the positive control group.
Conclusion: This study indicated that nano-drugs are more suitable for the treatment of dermatophytosis and could be considered as future alternatives for the treatment of dermatophytosis.
2. Castelo-Branco DSCM, Aguiar L, Araújo GDS, Lopes RGP, Sales JA, Pereira-Neto WA, et al. In vitro and ex vivo biofilms of dermatophytes: a new panorama for the study of antifungal drugs. Biofouling 2020;36:783-791.
3. Zareshahrabadi Z, Totonchi A, Rezaei‐Matehkolaei A, Ilkit M, Ghahartars M, Arastehfar A, et al. Molecular identification and antifungal susceptibility among clinical isolates of dermatophytes in Shiraz, Iran (2017–2019). Mycoses 2021;64:385-393.
4. Verma S, Madhu R. The great Indian epidemic of superficial dermatophytosis: an appraisal. Indian J Dermatol 2017;62:227-236.
5. Khosravi AR, Mahmoudi M. Dermatophytes isolated from domestic animals in Iran. Mycoses 2003;46:222-225.
6. Sharma P, Bhalla M, Thami GP, Chander J. Evaluation of efficacy and safety of oral terbinafine and itraconazole combination therapy in the management of dermatophytosis. J Dermatolog Treat 2020;31:749-753.
7. Nweze EI, Eke IE. Dermatophytes and dermatophytosis in the eastern and southern parts of Africa. Med Mycol 2018;56:13-28.
8. Gupta AK, Foley KA, Versteeg SG. New antifungal agents and new formulations against dermatophytes. Mycopathologia 2017;182:127-141.
9. Khurana A, Sardana K, Chowdhary A. Antifungal resistance in dermatophytes: recent trends and therapeutic implications. Fungal Genet Biol 2019;132:103255.
10. Nguyen CV, Collier S, Merten AH, Maguiness SM, Hook KP. Tinea capitis: a single‐institution retrospective review from 2010 to 2015. Pediatr Dermatol 2020;37:305-310.
11. Ferguson L, Fuller LC. Spectrum and burden of dermatophytes in children. J Infect 2017;74 Suppl 1:S54-S60.
12. Parsameher N, Rezaei S, Khodavasiy S, Salari S, Hadizade S, Kord M, et al. Effect of biogenic selenium nanoparticles on ERG11 and CDR1 gene expression in both fluconazole-resistant and -susceptible Candida albicans isolates. Curr Med Mycol 2017;3:16-20.
13. Sarrafha MR, Hashemi SJ, Rezaei S, Bayat M. In vitro evaluation of the effects of fluconazole and nano-fluconazole on Aspergillus Flavus and Aspergillus fumigatus isolates. Jundishapur J Microbiol 2018;11(6):e57875.
14. Shimamura T, Kubota N, Shibuya K. Animal model of dermatophytosis. J Biomed Biotechnol 2012;2012:125384.
15. Innis MA, Celfand DH, Sninsky JJ, White TJ (1990). PCR protocols: a guide to methods and applications. 1st ed. Academic Press. London.
16. Thekkangil A, George B, Prakash SMU, Suchithra TV. Mechanism of Streptomyces albidoflavus STV1572a derived 1-heneicosanol as an inhibitor against squalene epoxidase of Trichophyton mentagrophytes. Microb Pathog 2021;154:104853.
17. Song X, Wei YX, Lai KM, He ZD, Zhang HJ. In vivo antifungal activity of dipyrithione against Trichophyton rubrum on guinea pig dermatophytosis models. Biomed Pharmacother 2018;108:558-564.
18. El-Nesr OH, Yahiya SA, El-Gazayerly ON. Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes. Saudi Pharm J 2010;18:217-224.
19. Ahmed SA, de Hoog GS, Stevens DA, Fahal AH, van de Sande WW. In vitro antifungal susceptibility of coelomycete agents of black grain eumycetoma to eight antifungals. Med Mycol 2015;53:295-301.
20. Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 2003;55:329-347.
21. Wolf M, Klang V, Halper M, Stix C, Heuser T, Kotisch H, et al. Monoacyl-phospatidylcholine nanostructured lipid carriers: influence of lipid and surfactant content on in vitro skin permeation of flufenamic acid and fluconazole. J Drug Deliv Sci Technol 2017;41:419-430.
22. CLSI. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard. 2nd ed. CLSI document M38-A2. Wayne, PA: Clinical and Laboratory Standard Institute; 2008.
23. Rafat Z, Hashemi SJ, Saboor-Yaraghi AA, Pouragha B, Taheriniya A, Moosavi A, et al. A systematic review and meta-analysis on the epidemiology, casual agents and demographic characteristics of onychomycosis in Iran. J Mycol Med 2019;29:265-272.
24. Gupta AK, Cooper EA (2008). Dermatophytosis (Tinea) and other superficial fungal infections. In: Diagnosis and treatment of human mycoses. Eds, DR Hospenthal, MG Rinaldi. Humana Press, 1st ed. New Jersey, United States, pp. 255-381.
25. Moriello KA, Coyner K, Paterson S, Mignon B. Diagnosis and treatment of dermatophytosis in dogs and cats. Clinical Consensus Guidelines of the World Association for Veterinary Dermatology. Vet Dermatol 2017;28(3):266-e268.
26. Maeki M, Kimura N, Sato Y, Harashima H, Tokeshi M. Advances in microfluidics for lipid nanoparticles and extracellular vesicles and applications in drug delivery systems. Adv Drug Deliv Rev 2018;128:84-100.
27. Ganesan P, Narayanasamy D. Lipid nanoparticles: different preparation techniques, characterization, hurdles, and strategies for the production of solid lipid nanoparticles and nanostructured lipid carriers for oral drug delivery. Sustain Chem Pharm 2017;6:37-56.
28. Musavi Bafrui N, Hashemi Hazaveh SJ, Bayat M. In-vitro activity of nano fluconazole and conventional fluconazole against cinically important dermatophytes. Iran J Public Health 2020;49:1970-1976.
29. Motedayen N, Hashemi SJ, Rezaei S, Bayat M. In-vitro evaluation of antifungal activity of terbinafine and terbinafine nano-drug against clinical isolates of dermatophytes. Jundishapur J Microbiol 2018;11(5):e62351.
30. Paliwal R, Paliwal SR, Kenwat R, Kurmi BD, Sahu MK. Solid lipid nanoparticles: a review on recent perspectives and patents. Expert Opin Ther Pat 2020;30:179-194.
|Issue||Vol 13 No 5 (2021)|
|Trichophyton mentagrophytes; Nano-drugs; Terbinafine; Fluconazole; Guinea pig|
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|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|