EFFECT OF DIFFERENT ANTI-LEISHMANIAL DRUGS ON THE BEHAVIOR OF LIPOSOMES: ELASTICITY AND PENETRATION THROUGH HUMAN SKIN

PÉREZ, ANA P; ROMERO, EDER; PERALTA, MARÍA FLORENCIA; MARIA E OLIVERA ME; GUZMAN, MARIA LAURA; APEZTEGUIA, G; CARRER, DOLORES

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC). LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI). XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE) VII Reunión Anual de la Socieda; 2016

Cutaneous Leishmaniasis is a parasitic orphan disease, which cause ulcerative injuries, and may induce serious complications. Topical treatments would minimize the disease side effects and would enhance patient compliance. We propose the use of anti-Leishmania drugs carried on Soy phosphatidylcholine (SPC) and sodium cholate (NaChol) liposomes for topical administration of AmphotericinB (AmB), Imiquimod (Im) or Indole (Ind). It has been previously described that liposomes penetration in the skin is related to their flexibility. We hypothesize that there may be a correlation between the drugs carried and the membrane liposomes flexibility. Hence, we measured the effect of the candidate drugs on the liposomes flexibility and their skin permeation capabilities. Liposomes flexibility was studied by the determination of oils phosphates from extrusion (N=3). Flexible and non-flexible liposomes were used as references. Skin permeation and penetration assays were performed in Franz Cells with abdominal human skin (N=5). The drugs permeability coefficient (Kp) was calculated. The quantity of each of the drugs retained in epidermis (E) and dermis (D), and their penetration depth were determined by validated extraction and quantitation methods. Drug suspensions at equivalent concentrations of the liposomes were used as references (N=3). D penetration ratio (DR) (liposome D µg / reference D µg) was calculated for comparison purposes.In comparison with the flexible liposomes, the incorporation of Im did not produce significant changes in the phosphates quantitated (ANOVA, pIm>AmB. This order was correlated with the capacity of skin drugs penetration capabilities from their liposomes.Ind from flexible liposomes penetrates deeply into the skin in comparison with its solution reference, with most of the drug being found in the dermis. Im, which did not showed changes in the membrane elasticity, penetrated moderately into the skin, with most of the drug being found in the epidermis and a significant amount found in the dermis. AmB, which seemed to be the less flexible, was mostly retained in the epidermis, with very little amount of drug found in the dermis.