Mahshid Mostafavi - Ph.D. Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran
Iraj Sharifi - Professor, Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran
Saeedeh Farajzadeh - Professor, Department of Pediatric dermatology, Kerman University of Medical Sciences, Kerman, Iran
Payam Khazaeli - Associate Professor, Department of Pharmaceutics, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
Hamid Sharifi - Associate Professor, HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran.
Sina Kakooei - Ph.D. Candidate, Oral and Dental Diseases Research Center, Dental School, Kerman University of Medical Sciences, Kerman, Iran

Background: Leishmaniasis represents a major global health problem with a few effective therapeutic drugs.Objectives: This study aimed to evaluate the efficacy of glucantime and amphotericin B (AmB) encapsulated in niosome against cutaneous leishmaniasis (CL) using in vitro and in vivo models.Material and Methods: The niosomal formulations of the drugs alone and in combination were prepared and characterized. Subsequent to the examination of their cytotoxicity, their efficacy was evaluated using an in vitro MTT assay, macrophage model, flow cytometry, and gene expression profiling. For evaluation of therapeutic effect of niosomal combination on the lesion induced by Leishmania major in inbred BALB/c mice, the size of lesions and number of parasites in spleen was assessed.Results: The niosomal formulations demonstrated significantly greater inhibitory effects compared with the non-niosomal forms when the IC50 was considered. The niosomal combination showed an increase in the apoptotic values and gene expression levels of IL-12 and metacaspase and a decrease in the levels of IL-10 with a dose-response effect. The niosomal combination was also effective in reducing the lesion size and splenic parasite burden in mice.Conclusions: Our findings indicated that there is a synergistic effect between AmB and glucantime in niosomal form in the inhibition of intracellular and extracellular forms of L. tropica. Additionally, the in vivo results on L. major suggest that topical niosomal formulation could be useful in the treatment of CL.

Cutaneous leishmaniasis, Niosome, Amphotericin B, In vivo, In vitro