title: In vitro skin permeation and retention of paromomycin from liposomes for topical treatment of the cutaneous leishmaniasis.
abstract: Paromomycin (PA), a very hydrophilic antibiotic, has been tested as an alternative topical treatment against cutaneous leishmaniasis (CL). Although this treatment has shown promising results, it has not been successful in accelerating the recovery in most cases. This could be attributed to the low skin penetration of PA. Liposomal formulations usually provide sustained and enhanced drug levels in skin. The aim of this study was to prepare liposomal formulations containing PA and to investigate their potential as topical delivery systems of this antileishmanial. Large multilamellar vesicles (MLVs) were prepared by conventional solvent evaporation method. Large unilamellar vesicles (LUVs) were prepared by reverse-phase evaporation method. The lipids used were soybean phosphatidylcholine (PC) and PC:cholesterol (CH) (molar ratio 1:1). The skin permeation experiments across stripped and normal hairless mice skin were performed in modified Franz diffusion cells. The PA entrapment in LUV liposomes (20.4 +/- 2.2%) was higher than that observed for MLV liposomes (7.5 +/- 0.9%). Drug entrapment was 41.9 +/- 6.2% and 27.2 +/- 2.4% for PC and PC:CH LUV, respectively. The skin permeation was 1.55 +/- 0.31%, 1.29 +/- 0.40%, 0.20 +/- 0.08%, and 0.50 +/- 0.19% for PC LUV, PC:CH LUV, empty LUV +/- PA and aqueous solution, respectively. Controlled topical delivery, across stripped skin, was observed for PA entrapped in LUV liposomes.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Luciana S
authors.initials: LS
authors.lastname: Ferreira
authors.forename: Gilson A
authors.initials: GA
authors.lastname: Ramaldes
authors.forename: Elzíria A
authors.initials: EA
authors.lastname: Nunan
authors.forename: Lucas A M
authors.initials: LA
authors.lastname: Ferreira
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D066298:In Vitro Techniques; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000378:metabolism; D008081:Liposomes; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010303:Paromomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012869:Skin Absorption; D013997:Time Factors; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D008081:Liposomes; D014344:Trypanocidal Agents; D010303:Paromomycin