Effect of different anti-Leishmanial drugs in the behavior of liposomes: elasticity and penetration through human skin

PERALTA, MA F; GUZMÁN, MA. L; PEREZ AP; APEZTEGUIA G; OLIVERA MA E; ROMERO EL; CARRER, D C

Congreso; Reunión conjunta 2016 SAIC-SAI-SAFE-AACyTAL-NANOMEDar; 2016

SAIC-SAI-SAFE-AACyTAL-NANOMEDar

Cutaneous Leishmaniasis is a parasitic orphan disease whichcauses ulcerative injuries and may induce serious complications.Topical treatments would minimize drugs side effects and enhancepatient compliance. We propose the use of AmphotericinB (AmB),Imiquimod (Im) or Indole (Ind) carried on Soy phosphatidylcholine:sodium cholate liposomes for topical administration. The literatureshows that liposomes penetration in the skin is related to theirflexibility. We hypothesize a correlation between the drugs penetrationand the liposomes flexibility. Hence, we measured the effectof the candidate drugs on the liposomes flexibility and their skinpermeation capabilities. Liposomes flexibility was studied by extrusion.Skin penetration assays were performed in Franz Cells withabdominal human skin. The drugs permeability coefficient (Kp) wascalculated. The quantity of drug retained in epidermis and dermisand the penetration depth were determined by validated methods.Drug suspensions at equivalent concentrations of the liposomeswere used as references. D penetration ratio (DR) (liposome Dμg/ reference D μg) was calculated for comparison purposes. Theincorporation of Im did not produce significant changes in the flexibilityof liposomes (ANOVA, p>0.05), however an increase in flexibilitywas determined from Ind-liposomes. Formulations containingAmB could not be extruded at the working pressure, possibly dueto a decrease in liposomes elasticity. All of the drugs assayedreached the dermis. Kp could only be determined for Ind systems.Ind from liposomes penetrates deeply into the skin in comparisonwith its reference (DR=1.7), with most of the drug being found indermis. Im penetrated moderately into the skin, with most of thedrug being found in epidermis and a significant amount found indermis (DR=0.8). AmB was mostly retained in epidermis, withvery little amount of drug found in dermis (DR=0.1). Liposomecontainingdrugs showed a flexibility with the order Ind>Im>AmB.This order correlates with drugs penetration into the skin.