1,2-Distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine (
DSHemsPC) is a new
lipid in which two molecules of
stigmasterol (an inexpensive
plant sterol) are covalently linked via a
succinic acid to glycerophosphocholine. Our previous study revealed that
liposome (Lip)-intercalated
amphotericin B (AMB) prepared from
DSHemsPC (
DSHemsPC-AMB-Lip) possesses excellent colloidal properties and in vitro antifungal and antileishmanial activities similar to those of the liposomal AMB preparation
AmBisome. The aim of this study was to determine the biodistribution and evaluate the antileishmanial effects of
DSHemsPC-AMB-Lip in Leishmania major-infected BALB/c mice. The serum profile and tissue concentrations of AMB were similar in
DSHemsPC-AMB-Lip- and
AmBisome-treated mice after intravenous (i.v.) injection. Multiple i.v. doses of the micellar formulation of AMB (
Fungizone; 1 mg/kg of
body weight),
DSHemsPC-AMB-Lip (5 mg/kg), and
AmBisome (5 mg/kg) were used in L. major-infected BALB/c mouse models of early and established lesions. In a model of the early lesions of
cutaneous leishmaniasis (CL), the results indicated that the level of footpad
inflammation was significantly (P < 0.001) lower in mice treated with
DSHemsPC-AMB-Lip and
AmBisome than mice treated with empty
liposomes or 5%
dextrose. The splenic and footpad parasite load was also significantly (P < 0.001) lower in these groups of mice than in control mice that received 5% DW or free
liposome. The in vivo activity of
DSHemsPC-AMB-Lip was comparable to that of
AmBisome, and both provided improved results compared to those achieved with
Fungizone at the designated doses. The results suggest that systemic
DSHemsPC-AMB-Lip administration may be useful for the treatment of
leishmaniasis, and because it costs less to produce
DSHemsPC-AMB-Lip than
AmBisome,
DSHemsPC-AMB-Lip merits further investigation.