title: An amphotericin B-based drug for treating experimental Leishmania major infection.
abstract: There is an urgent need for a non-toxic and low-cost treatment for cutaneous leishmaniasis. We synthesised and tested in vivo an amphotericin B-poly(methacrylic acid) drug (AmB-PMA) that had previously shown in-vitro activity against Leishmania major and L. donovani parasites. Efficacy was determined using L. major footpad infection in 30 non-healing BALB/c mice. Three subcutaneous injections of AmB-PMA at days 7, 14 and 21 post-infection resulted in a reduction of ∼80% in lesion size by day 35 post-infection in 18 treated mice compared with six untreated controls, and complete healing of lesions by day 50 with no lesion relapse seen at day 80 post-infection in six treated mice. Healing was associated with decreased IL-10 (P=0.002) and increased IFN-γ (P=0.005) in the footpad.
authors.affiliation: Department of Infectious Diseases & Immunity, Imperial College London, UK.
authors.forename: Karina D
authors.initials: KD
authors.lastname: Corware
authors.forename: Matthew
authors.initials: M
authors.lastname: Rogers
authors.forename: Ian
authors.initials: I
authors.lastname: Teo
authors.forename: Ingrid
authors.initials: I
authors.lastname: Müller
authors.forename: Sunil
authors.initials: S
authors.lastname: Shaunak
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D018320:Leishmania major / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000913:Antibodies, Protozoan; D000981:Antiprotozoal Agents; D000666:Amphotericin B