Topical delivery and in vivo antileishmanial activity of paromomycin-loaded liposomes for treatment of cutaneous leishmaniasis

• Published in: Journal of liposome research Vol. 20; no. 1; pp. 16 - 23
• Main Authors: Carneiro, Guilherme, Santos, Delia C.M., Oliveira, Monica C., Fernandes, Ana P., Ferreira, Luciana S., Ramaldes, Gilson A., Nunan, Elziria A., Ferreira, Lucas A.M.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01-03-2010; Taylor & Francis
• Subjects: Administration, Topical; Animals; Cholesterol - metabolism; Cholesterol - therapeutic use; cutaneous leishmaniasis; Female; Leishmaniasis, Cutaneous - drug therapy; Leishmaniasis, Cutaneous - metabolism; liposomes; Liposomes - metabolism; Liposomes - therapeutic use; Mice; Mice, Inbred BALB C; Paromomycin; Paromomycin - administration & dosage; Paromomycin - metabolism; Paromomycin - therapeutic use; Particle Size; Phosphatidylcholines - metabolism; Phosphatidylcholines - therapeutic use; Skin - metabolism; topical delivery; topical treatment
• ISSN: 0898-2104; 1532-2394
• DOI: 10.3109/08982100903015025

The present study aimed to evaluate the potential of liposomes loaded with paromomycin (PA), an aminoglycoside antibiotic associated with poor skin penetration, for the topical treatment of cutaneous leishmaniasis (CL). Fluid liposomes were prepared and characterized for particle size, zeta potential, and drug entrapment. Permeation studies were performed with two in vitro models: intact and stripped skin. The antileishmanial activity of free and liposomal PA was evaluated in BALB/c mice infected by Leishmania (L.) major. Drug entrapment ranged from 10 to 14%, and the type of vesicle had little influence on this parameter. Particle size and polydispersity index of the vesicles composed by phosphatidylcholine (PC) and PC/cholesterol (Chol) ranged from of 516 to 362 nm and 0.7 to 0.4, respectively. PA permeation across intact skin was low, regardless of the formulation tested, while drug penetration into skin (percent of the applied dose) from PC (7.2 ± 0.2%) and PC/Chol (4.8 ± 0.2%) liposomes was higher than solution (1.9 ± 0.1%). PA-loaded liposomes enhanced in vitro drug permeation across stripped skin and improved the in vivo antileishmanial activity in experimentally infected mice. Our findings suggest that the liposomes represent a promising alternative for the topical treatment of CL using PA.