Nanoemulsified Butenafine for Enhanced Performance against Experimental Cutaneous Leishmaniasis

Author(s)

Bezerra-Souza, Adriana ^[1] ; Jesus, Jessica A. ^[1] ; Laurenti, Marcia D. ^[1] ; Lalatsa, Aikaterini ^[2] ; Serrano, Dolores R. ^{[3, 4]} ; Passero, Luiz Felipe D. ^{[5, 6]}

Affiliation

^[1] Univ Sao Paulo, Med Sch, Lab Pathol Infect Dis LIM 50, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

^[2] Univ Portsmouth, Sch Pharm & Biomed Sci, Inst Biomed & Biomol Sci, Biomat Bioengn & Nanomed BioN Lab, White Swan Rd, Portsmouth PO1 2DT, Hants - England

^[3] Univ Complutense Madrid, Sch Pharm, Dept Pharmaceut & Food Technol, Madrid 28040 - Spain

^[4] Univ Complutense Madrid, Sch Pharm, Inst Univ Farm Ind IUFI, Madrid 28040 - Spain

^[5] Sao Paulo State Univ UNESP, Inst Biosci, Praca Infante Dom Henrique S-N, BR-11330900 Sao Vicente, SP - Brazil

^[6] Sao Paulo State Univ UNESP, Inst Adv Studies Ocean, Av Joao Francisco Bensdorp 1178, BR-11350011 Sao Vicente, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF IMMUNOLOGY RESEARCH; v. 2021, MAR 31 2021.
• Web of Science Citations: 0

Abstract

The production of ergosterol lipid involves the activity of different enzymes and is a crucial event for the Leishmania membrane homeostasis. Such enzymes can be blocked by azoles and allylamines drugs, such as the antifungal butenafine chloride. This drug was active on parasites that cause cutaneous and visceral leishmaniasis. Based on the leishmanicidal activity of butenafine chloride and considering the absence of reports about the therapeutic potential of this drug in cutaneous leishmaniasis, the present work is aimed at analyzing the efficacy of butenafine formulated in two different topical delivery systems, the self-nanoemulsifying drug delivery systems (BUT-SNEDDS) and in a SNEDDS-based nanogel (BUT-SNEDDS gel) as well as in the free form in experimental cutaneous leishmaniasis. Physical studies showed that both formulations were below 300 nm with low polydispersity (<0.5) and good colloidal stability (around -25 mV). Increased steady-state flux was reported for nanoenabled butenafine formulations with reduced lag time in Franz cell diffusion assays across Strat-M membranes. No toxic or inflammatory reactions were detected in animals treated with BUT-SNEDDS, BUT-SNEDDS gel, or butenafine. Animals topically treated with butenafine (free or nanoformulated) showed small dermal lesions and low tissue parasitism. Furthermore, BUT-SNEDD gel and butenafine presented similar efficacy than the standard drug Glucantime given by the intralesional route. Increased levels of IFN-gamma were observed in animals treated with BUT-SNEDDS gel or butenafine. Based on these data, the antifungal drug butenafine chloride can be considered an interesting repurposed drug for the treatment of cutaneous leishmaniasis. (AU)

• FAPESP's process: 16/00468-0 - Use of drug repurposing and natural product bioprospection to characterize compounds with in vitro and in vivo leishmanicidal action
• Grantee: Luiz Felipe Domingues Passero
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/24077-6 - Pre-clinical studies of non-invasive treatments in leishmaniasis
• Grantee: Luiz Felipe Domingues Passero
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/09405-4 - Evaluation of the therapeutic effect of butenafine in the American Tegumentar Leishmaniasis
• Grantee: Adriana Bezerra de Souza
• Support Opportunities: Scholarships in Brazil - Master