title: In-vitro and in-vivo studies on a topical formulation of sitamaquine dihydrochloride for cutaneous leishmaniasis.
abstract: The efficacy of topical formulations of the 8-aminoquinoline, sitamaquine dihydrochloride, in both in-vitro and in in-vivo models of cutaneous leishmaniasis is reported. In-vitro parasite assays confirmed that sitamaquine dihydrochloride was active against a range of Leishmania species that cause either cutaneous or visceral leishmaniasis, with ED50 values against amastigotes over the range of 2.9 to 19.0 microM. A range of topical sitamaquine dihydrochloride formulations (anhydrous gel, emulsions) were developed for studies on experimental cutaneous leishmaniasis using only topically acceptable excipients or those currently undergoing regulatory approval. An uptake study into murine skin confirmed in-vitro skin penetration and retention. Several formulations were tested in-vivo against Leishmania major cutaneous lesions in BALB/c mice. None of the sitamaquine dihydrochloride formulations tested appeared to either slow lesion progression or reduce parasite burden.
authors.affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Tracy
authors.initials: T
authors.lastname: Garnier
authors.forename: Marc B
authors.initials: MB
authors.lastname: Brown
authors.forename: M Jayne
authors.initials: MJ
authors.lastname: Lawrence
authors.forename: Simon L
authors.initials: SL
authors.lastname: Croft
mesh_terms: D000287:Administration, Topical; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007891:Leishmania / Q000187:drug effects; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008264:Macrophages / Q000469:parasitology; D008543:Melanins / Q000378:metabolism; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D012869:Skin Absorption
chemical_list: D000634:Aminoquinolines; D000981:Antiprotozoal Agents; D008543:Melanins; C080436:8-aminoquinoline