02698nas a2200385 4500000000100000008004100001260001300042653003000055653001200085653001400097653001400111653001100125653002100136653002900157653001400186653000900200653002400209653001600233653001800249653000900267653001100276100001400287700001500301700001500316700001300331700001400344700001500358700001400373700001800387245013500405300001200540490000700552520173900559022001402298 2009 d c2009 Jun10aAdministration, Cutaneous10aAnimals10aCell Line10aDiffusion10aFemale10aLeishmania major10aLeishmaniasis, Cutaneous10aLiposomes10aMice10aMice, Inbred BALB C10aParomomycin10aParticle Size10aSkin10aSpleen1 aJaafari M1 aBavarsad N1 aBazzaz BSF1 aSamiei A1 aSoroush D1 aGhorbani S1 aHeravi ML1 aKhamesipour A00aEffect of topical liposomes containing paromomycin sulfate in the course of Leishmania major infection in susceptible BALB/c mice. a2259-650 v533 a

The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomycin sulfate (PM) in Leishmania major-infected BALB/c mice. Liposomes containing 10 or 15% PM (Lip-PM-10 and Lip-PM-15, respectively) were prepared by the fusion method and were characterized for their size and encapsulation efficiency. The penetration of PM from the liposomal PM formulations (LPMFs) through and into skin was evaluated in vitro with Franz diffusion cells fitted with mouse skin at 37 degrees C for 8 h. The in vitro permeation data showed that almost 15% of the LPMFs applied penetrated the mouse skin, and the amount retained in the skin was about 60% for both formulations. The 50% effective doses of Lip-PM-10 and Lip-PM-15 against L. major promastigotes in culture were 65.32 and 59.73 microg/ml, respectively, and those against L. major amastigotes in macrophages were 24.64 and 26.44 microg/ml, respectively. Lip-PM-10 or Lip-PM-15 was used topically twice a day for 4 weeks to treat L. major lesions on BALB/c mice, and the results showed a significantly (P < 0.001) smaller lesion size in the mice in the treated groups than in the mice in the control group, which received either empty liposomes or phosphate-buffered saline (PBS). Eight weeks after the beginning of the treatment, every mouse treated with LPMFs was completely cured. The spleen parasite burden was significantly (P < 0.001) lower in mice treated with Lip-PM-10 or Lip-PM-15 than in mice treated with PBS or control liposomes, but no significant difference was seen between the two groups treated with either Lip-PM-10 or Lip-PM-15. The results suggest that topical liposomal PM may be useful for the treatment of cutaneous leishmaniasis.

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