Nanoemulsified butenafine for enhanced performance against experimental cutaneous leishmaniasis

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 (in vitro) on parasites that cause cutaneous and visceral leishmaniasis. Based on the leishmanicidal activity of butenafine and considering the absence of reports about the therapeutic potential of this drug in cutaneous leishmaniasis, the present work aimed at analyzing the efficacy of butenafine chloride formulated in two different topical delivery systems, the self-nanoemulsifying drug delivery systems (SNEDD) and in a SNEDD-based nanogel (nanogel) as well as in the free form in murine cutaneous leishmaniasis. Physical studies showed that both nanoformulations were below 300nm, showed low polydispersity (< 0.5) and high degree of stability (< -25mV), additionally nanoformulations and free butenafine were able to permeate the skin of healthy mice, without cause toxic or inflammatory reactions. Animals topically treated with butenafine (free or nanoformulated) showed low skin lesion and tissue parasitism. Furthermore, butenafine loaded in nanogel or administered in the free form presented similar efficacy than the standard treatment, performed by the intralesional route with glucantime. Increased levels of IFN-γ were associated to the treatment performed with butenafine loaded in nanogel or in the free form. Based on these data, the antifungal drug butenafine chloride can be considered an interesting repurposed drug for the treatment of cutaneous leishmaniasis.