Biodistribution and in vivo antileishmanial activity of 1,2-distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine liposome-intercalated amphotericin B

Iman, M. and Huang, Z. and Alavizadeh, S. H. and Szoka, F. C. and Jaafarib, M. R. (2017) Biodistribution and in vivo antileishmanial activity of 1,2-distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine liposome-intercalated amphotericin B. Antimicrobial Agents and Chemotherapy, 61 (9).

[img] Text
Biodistribution and In Vivo Antimicrobial Agents and Chemotherapy.pdf

Download (2MB)


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 majorinfected 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. Copyright © 2017 American Society for Microbiology. All Rights Reserved.

Item Type: Article
Additional Information: Cited By :6 Export Date: 16 February 2020 CODEN: AMACC Correspondence Address: Jaafarib, M.R.; Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical SciencesIran; email:
Uncontrolled Keywords: amphotericin B Biodistribution Distigmasteryl-modified phospholipids Leishmaniasis Liposomes 1,2-distigmasterylhemisuccinoyl-glycero-3-phosphocholine amphotericin B lipid complex antiprotozoal agent drug carrier liposome phosphatidylcholine stigmasterol analogs and derivatives animal Bagg albino mouse disease model drug administration route drug effect female Leishmania major mouse parasite load parasitology pathogenicity skin leishmaniasis spleen Animals Antiprotozoal Agents Disease Models, Animal Drug Administration Routes Drug Carriers Leishmaniasis, Cutaneous Mice Mice, Inbred BALB C Phosphatidylcholines
Subjects: QU Biochemistry
QV pharmacology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib3 lib3
Date Deposited: 28 Apr 2020 08:17
Last Modified: 28 Apr 2020 08:17

Actions (login required)

View Item View Item