title: Development of antileishmanial lipid nanocomplexes.
abstract: Visceral leishmaniasis is a life-threatening disease that affects nearly a million people every year. The emergence of Leishmania strains resistant to existing drugs complicates its treatment. The purpose of this study was to develop a new lipid formulation based on nanocochleates combining two active drugs: Amphotericin B (AmB) and Miltefosine (HePC). Nanocochleates composed of dioleoylphosphatidylserine (DOPS) and Cholesterol (Cho) and Ca(2+), in which HePC and AmB were incorporated, were prepared. Properties such as particle size, zeta potential, drug payload, in-vitro drug release and storage stability were investigated. Moreover, in-vitro stability in gastrointestinal fluid was performed in view of an oral administration. AmB-HePC-loaded nanocochleates with a mean particle size of 250 ± 2 nm were obtained. The particles displayed a narrow size distribution and a drug payload of 29.9 ± 0.5 mg/g for AmB, and 14.0 ± 0.9 mg/g for HePC. Drug release occurred preferentially in intestinal medium containing bile salts. Therefore, AmB-HePC-loaded nanocochleates could be a promising oral delivery system for the treatment of visceral leishmaniasis.
authors: Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay Malabry Cedex, France; Groupe Chimiothérapie Antiparasitaire, UMR 8076 CNRS, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay Malabry Cedex, France.
authors: T T H
authors: TT
authors: Pham
authors: Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay Malabry Cedex, France.
authors: C
authors: C
authors: Gueutin
authors: Laboratoire Acides Nucléïques et Biophotonique ANBIOPHY, FRE 3207 CNRS, Université Pierre et Marie Curie, 75252 Paris Cedex, France.
authors: M
authors: M
authors: Cheron
authors: Groupe de Chimie Analytique de Paris-Sud, EA4041, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay Malabry Cedex, France.
authors: S
authors: S
authors: Abreu
authors: Groupe de Chimie Analytique de Paris-Sud, EA4041, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay Malabry Cedex, France.
authors: P
authors: P
authors: Chaminade
authors: Groupe Chimiothérapie Antiparasitaire, UMR 8076 CNRS, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay Malabry Cedex, France.
authors: P M
authors: PM
authors: Loiseau
authors: Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay Malabry Cedex, France. Electronic address: gillian.barratt@u-psud.fr.
authors: G
authors: G
authors: Barratt
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000737:chemistry*; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D002118:Calcium / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D002942:Circular Dichroism; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D006801:Humans; D007898:Leishmaniasis, Visceral / Q000469:parasitology / Q000517:prevention & control; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D046529:Microscopy, Electron, Transmission; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010718:Phosphatidylserines / Q000737:chemistry; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D013053:Spectrophotometry
chemical_list: D000981:Antiprotozoal Agents; D008055:Lipids; D008081:Liposomes; D010718:Phosphatidylserines; D010767:Phosphorylcholine; C039128:miltefosine; C042511:1,2-dioleoylphosphatidylserine; D000666:Amphotericin B; D002784:Cholesterol; D002118:Calcium
keywords: Amphotericin B; Miltefosine; Nanocochleates; Oral route; Visceral leishmaniasis