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Antimicrobial Agents and Chemotherapy, June 2009, p. 2259-2265, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.01319-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Effect of Topical Liposomes Containing Paromomycin Sulfate in the Course of Leishmania major Infection in Susceptible BALB/c Mice{triangledown}

Mahmoud R. Jaafari,1* Neda Bavarsad,1 Bibi Sedigheh Fazly Bazzaz,1 Afshin Samiei,1 Dina Soroush,1 Serajodin Ghorbani,1 Mohammad M. Lotfi Heravi,1 and Ali Khamesipour2

School of Pharmacy, Biotechnology Research Center and Pharmaceutical Research Center, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran,1 Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran2

Received 2 October 2008/ Returned for modification 18 November 2008/ Accepted 6 February 2009

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°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 µg/ml, respectively, and those against L. major amastigotes in macrophages were 24.64 and 26.44 µg/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.

* Corresponding author. Mailing address: School of Pharmacy, Biotechnology Research Center and Pharmaceutical Research Center, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran. Phone: 98 511 8823252. Fax: 98 511 8823251. E-mail: jafarimr{at}mums.ac.ir

{triangledown} Published ahead of print on 17 February 2009.

Antimicrobial Agents and Chemotherapy, June 2009, p. 2259-2265, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.01319-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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