Efficacy of topical miltefosine formulations in an experimental model of cutaneous leishmaniasis

PERALTA MA.F.; GUZMÁN MA.L.; BARROSO, P.A.; USSEGLIO, NADINA; OLIVERA, MA.E.; CARRER, D. C.; BRACAMONTE, MA. E.; MARCO, J.D.

Drug Delivery and Translational Research

Springer

Año: 2021 p. 180 - 196

2190-393X

Cutaneous leishmaniasis (CL) is a neglected tropical disease endemic in ~90 countries, with an increasing incidence. Currently available pharmacotherapy implies the systemic administration of moderately/very toxic drugs. Miltefosine (Milt) is the only FDA approved drug to treat CL via the oral route (Impavido ®). It produces side effects; in particular, teratogenic effects are of concern. A topical treatment would have the great advantage of minimising the systemic circulation of the drug, preventing side effects. We prepared dispersions containing Milt and liposomes of different compositions to enhance/modulate trans-epidermal penetration and evaluated in vitroand in vivo efficacy and toxicity , in vitro release rate of the drug and particles size stability with time. Treatments were topically administered to BALB/c mice infected with Leishmania (Leishmania) amazonensis . The dispersions containing 0.5 % Milt eliminated 99 % of the parasites and cured the lesions with a complete reepithelisation, no visible scar and re-growth of hair. Fluid liposomes decreased the time to heal the lesion and the time needed to eliminate viable amastigotes from the lesion site. Relapse of the infection was not found one month after treatment in any case. Ultraflexible liposomes on the other hand had no significant in vitro effect but decreased in vivo efficacy. A topical Milt formulation including fluid liposomes seemsa promising treatment against CL