Anti-leishmanial drugs in liposomes: effect on elasticity and penetration through human and mouse skin

PERALTA MA.F.; GUZMÁN M.L.; APEZTEGUIA G.; ANA PAULA PEREZ; ROMERO E.L.; OLIVERO M.E.; CARRER, D. C.

Conferencia; Nanomercosur 2017; 2017

Fundacion Argentina de Nanotecnologia

Leishmaniasis is one of six Tropical Orphan Diseases catalogued as most important by WHO.Cutaneous Leishmaniasis (CL) is one of the forms of the disease, affecting between 0.7 and 1.2million people worldwide. There is a strong need of new and better ways of treatment. Most antileishmanialdrugs have serious side effects that limit their systemic use. Topical treatments have theadvantages of having few adverse effects, better patient compliance and greater feasibility of use ina rural environment. In particular, the use of ultraflexible liposomes of nanometric size is of interestdue to their proven capacity of enhancing transepidermal penetration. This capacity is proposed tobe dependent on the flexibility of the lipidic membrane. We have thus studied the effect of threeanti-leishmanial drugs on Soy Phosphatidylcholine:Na Cholateliposomes stability and flexibility,while at the same time evaluating the transepidermal penetration both of the lipidic components ofthe liposomes and of the drugs. AmphotericinB (AmB), Imiquimod (Imiq) and Indole (Ind) wereincorporated into the liposomal formulations. None of the drugs affected the size of the liposomes.Deformability was only slightly changed. The penetration of the lipidic components of theformulations was studied in BalbC mice in vivo by confocal fluorescence microscopy. Canyons arethe structure of preference for skin penetration of lipids, independently of the incorporated drug.Also, the lipids in vivo penetrated the skin to the same depths regardless of the drug incorporated inthe liposomes. On the other hand, permeability of drugs from liposomal dispersions was studied inhuman skin ex vivo. In this experiment, ultra-flexible liposomes produced enhancement of drugspenetration into/through human skin in all cases in comparison with fluid liposomes withoutdetergent, regardless of drug molecular weight