Amphotericin B (AmB) has a broad antifungal and leishmanicidal activity with low incidence of clinical resistance. Its parenteral administration has high risk of nephrotoxicity that limits its use. In order to treat cutaneous
infections, AmB
topical administration is a safer
therapy because of the low systemic absorption of the
drug across mucous membranes. Moreover, in some developing countries both fungal topical
infections and
cutaneous leishmaniasis are an important health problem. The aim of this work is to formulate a topical
amphotericin preparation and test its in vitro antifungal (against 11 different fungal species) and antileishmanial activity. γ-
Cyclodextrin (γ-CD) was chosen to solubilise AmB. Furthermore, γ-CD has shown a synergistic effect on membrane destabilization with AmB. Topical novel formulations based on AmB-CD complex have exhibited greater antifungal activity (48%, 28% and 60% higher) when compared to AmB Neo-Sensitabs(®) disks, AmB dissolved in
dimethyl sulfoxide (
DMSO) and
Clotrimazole(®) cream, respectively. Furthermore, AmB-CD
methyl cellulose gel has shown significantly higher inhibition activity on biofilm formation, larger penetration through yeast biofilms and higher fungicidal activity on biofilm cells compared to AmB dissolved in
DMSO. In addition, AmB-CD gel exhibited both high in vitro leishmanicidal efficacy with wider therapeutic index (between 2 and 8-fold higher than AmB
deoxycholate depending on Leishmania spp.) and also in vivo activity in an experimental model of
cutaneous leishmaniasis. These results illustrate the feasibility of a topical AmB formulation easy to prepare, physicochemically stable over 6 months, safe and effective against diverse fungal and parasitic cutaneous
infections.