title: Strategies for the design of orally bioavailable antileishmanial treatments.
abstract: Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. The most serious, life-threatening form is visceral leishmaniasis (VL). No vaccine is yet available for human use and chemotherapy is the main mean of dealing with this disease. This review focuses on the development of drug delivery systems (DDS) for treatment of leishmaniasis. After an overview of the significance of leishmaniasis in 2013, current chemotherapy and its limitations are considered, leading to possible strategies to improve the treatment of VL: new drugs, combinations of existing drugs and DDS, particularly for oral administration. Nanostructured biomaterials such as lipid-based or polymeric nanoparticles have unique physicochemical properties, ultra-small and controllable size, large surface area to mass ratio and the possibility of surface modification which can be used to advantage for the oral administration of antileishmanial drugs. They can improve the rate of dissolution of poorly water-soluble drugs, increase intestinal residence time by bioadhesion and, especially when lipid additives are used, influence the route and efficiency of absorption. These recent advances in this very active field should lead to better management of this serious disease.
authors.affiliation: Institut Galien Paris-Sud, UMR CNRS 8612, Faculté de Pharmacie, Université Paris XI, 92296 Châtenay Malabry Cedex, France.
authors.forename: T T H
authors.initials: TT
authors.lastname: Pham
authors.forename: P M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: G
authors.initials: G
authors.lastname: Barratt
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D015195:Drug Design; D004359:Drug Therapy, Combination; D006801:Humans; D007408:Intestinal Absorption; D007896:Leishmaniasis / Q000175:diagnosis / Q000188:drug therapy* / Q000469:parasitology; D053758:Nanoparticles; D036103:Nanotechnology; D012995:Solubility
chemical_list: D000981:Antiprotozoal Agents
keywords: AmB; CL; DDS; Drug combinations; HePC; Nanoparticles; Oral administration; VL; Visceral leishmaniasis; amphotericin B; cutaneous leishmaniasis; drug delivery system; hexadecylphosphocholine (miltefosine); visceral leishmaniasis