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Development of topical liposomes containing miltefosine for the treatment of Leishmania major infection in susceptible BALB/c mice

Kavian, Zahra, Alavizadeh, Seyedeh Hoda, Golmohamadzadeh, Shiva, Badiee, Ali, Khamesipour, Ali, Jaafari, Mahmoud Reza
Acta tropica 2019 v.196 pp. 142-149
Leishmania major, antileishmanial properties, culture media, cutaneous leishmaniasis, mice, parasites, topical application
Herein, we investigated the efficacy of liposomes for the topical delivery of miltefosine (ML) to treat cutaneous leishmaniasis (CL). Liposomes containing varying concentrations of ML (0.5, 1, 2 and 4%) were prepared and characterized by their size and entrapment efficiency. The liposome diameters were between 100–150 nm. The penetration of ML from liposomal formulations through and in the skin was assessed using ex-vivo Franz diffusion cells fitted with mouse skin at 37 °C for 24 h. Data indicated that Lip-ML-4% showed the highest percent of retention across mouse skin (82%). in vitro promastigote and amastigote assays showed that ML and Lip-ML inhibit the growth of parasites either in the culture medium or intracellularly. Lip-ML formulations were topically applied twice a day for 4 weeks to the skin of BALB/c mice infected with L. major. Results showed a significantly (p < 0.001) smaller lesion size in Lip-ML-2 and 4% when compared to controls. At week 8 post-infection, the number of parasites was higher in Lip-ML-0.5% compared to Lip-ML-2 and 4%, however, the difference was not significant. At week 12, the splenic parasite burden was significantly (p < 0.001) lower in mice treated with different Lip-ML formulations when compared to controls. The lesion parasite burden was significantly (p < 0.001) lower in mice treated with either Lip-ML-2 and 4% compared to Lip-ML-0.5% at week 12 post-infection. The results suggested that topical Lip-ML-4% showed optimal ex-vivo penetration and in vivo anti-leishmanial activity against CL caused by L. major when compared to ML cream and other liposomes and thus, merits further investigation.