Efficacy of topical Miltefosine formulations in an experimental model of cutaneous leishmaniasis.

Autor: Peralta, Ma. Florencia, Usseglio, Nadina A., Bracamonte, Ma. Estefanía, Guzmán, Ma. Laura, Olivera, Ma. Eugenia, Marco, J. Diego, Barroso, Paola A., Carrer, Dolores C.
Zdroj: Drug Delivery & Translational Research; Jan2022, Vol. 12 Issue 1, p180-196, 17p
Abstrakt: Cutaneous leishmaniasis (CL) is a neglected tropical disease endemic in ~ 90 countries, with an increasing incidence. Presently 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 vitro and 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 re-epithelisation, 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 1 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 seems a promising treatment against CL. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index