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

Autor: Peralta MF; Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC- CONICET- UNC, 5016, Córdoba, Argentina., Usseglio NA; Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC- CONICET- UNC, 5016, Córdoba, Argentina.; Departamento de Ciencias Farmacéuticas, UNITEFA - CONICET - Universidad Nacional de Córdoba, 5016, Córdoba, Argentina., Bracamonte ME; Instituto de Patología Experimental - CONICET - , Universidad Nacional de Salta, 4400, Salta, Argentina., Guzmán ML; Departamento de Ciencias Farmacéuticas, UNITEFA - CONICET - Universidad Nacional de Córdoba, 5016, Córdoba, Argentina., Olivera ME; Departamento de Ciencias Farmacéuticas, UNITEFA - CONICET - Universidad Nacional de Córdoba, 5016, Córdoba, Argentina., Marco JD; Instituto de Patología Experimental - CONICET - , Universidad Nacional de Salta, 4400, Salta, Argentina., Barroso PA; Instituto de Patología Experimental - CONICET - , Universidad Nacional de Salta, 4400, Salta, Argentina., Carrer DC; Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC- CONICET- UNC, 5016, Córdoba, Argentina. dolorescarrer@immf.uncor.edu.
Jazyk: angličtina
Zdroj: Drug delivery and translational research [Drug Deliv Transl Res] 2022 Jan; Vol. 12 (1), pp. 180-196. Date of Electronic Publication: 2021 Jan 27.
DOI: 10.1007/s13346-021-00896-8
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.
(© 2021. Controlled Release Society.)
Databáze: MEDLINE
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