OBJECTIVES: The efficacy of different formulations of the naphthoquinone buparvaquone and two phosphate prodrugs in in vivo models of both visceral and cutaneous leishmaniasis is described. METHODS: Several topical formulations of buparvaquone containing acceptable excipients were tested in vivo against Leishmania major cutaneous lesions in BALB/c mice. In vivo studies against Leishmania donovani investigated whether the prodrugs had improved efficacy when compared with buparvaquone. RESULTS: Both a hydrous gel and water-in-oil emulsion of buparvaquone significantly reduced cutaneous parasite burden (P < 0.05, 22 days post-infection) and lesion size, compared with the untreated control (P < 0.0001, 16 days post-infection). The prodrug 3-phosphonooxymethyl-buparvaquone was formulated into an anhydrous gel and this also significantly reduced parasite burden and lesion size (P < 0.0001, 16 days post-infection). Histology confirmed this efficacy. In the visceral model, both prodrugs were significantly more effective at reducing liver parasite burden than the parent drug, buparvaquone. Buparvaquone-3-phosphate was shown to be the most effective antileishmanial (P = 0.0003, 50 mg buparvaquone molar equivalent/kg/day five times), reducing the liver parasite burden by approximately 34% when compared with the untreated control. CONCLUSIONS: The introduction of a topical formulation, such as buparvaquone (or its prodrug), would be a significant advance for the treatment of simple cutaneous lesions. In particular, the avoidance of the parenteral antimonials would greatly increase patient compliance and reduce treatment costs.
OBJECTIVES: The efficacy of different formulations of the naphthoquinonebuparvaquone and two phosphate prodrugs in in vivo models of both visceral and cutaneous leishmaniasis is described. METHODS: Several topical formulations of buparvaquone containing acceptable excipients were tested in vivo against Leishmania major cutaneous lesions in BALB/c mice. In vivo studies against Leishmania donovani investigated whether the prodrugs had improved efficacy when compared with buparvaquone. RESULTS: Both a hydrous gel and water-in-oil emulsion of buparvaquone significantly reduced cutaneous parasite burden (P < 0.05, 22 days post-infection) and lesion size, compared with the untreated control (P < 0.0001, 16 days post-infection). The prodrug 3-phosphonooxymethyl-buparvaquone was formulated into an anhydrous gel and this also significantly reduced parasite burden and lesion size (P < 0.0001, 16 days post-infection). Histology confirmed this efficacy. In the visceral model, both prodrugs were significantly more effective at reducing liver parasite burden than the parent drug, buparvaquone. Buparvaquone-3-phosphate was shown to be the most effective antileishmanial (P = 0.0003, 50 mg buparvaquone molar equivalent/kg/day five times), reducing the liver parasite burden by approximately 34% when compared with the untreated control. CONCLUSIONS: The introduction of a topical formulation, such as buparvaquone (or its prodrug), would be a significant advance for the treatment of simple cutaneous lesions. In particular, the avoidance of the parenteral antimonials would greatly increase patient compliance and reduce treatment costs.
Authors: Marta Gontijo Aguiar; Aline Márcia Machado Pereira; Ana Paula Fernandes; Lucas Antonio Miranda Ferreira Journal: Antimicrob Agents Chemother Date: 2010-08-16 Impact factor: 5.191
Authors: Claire J Forbes; Deborah Lowry; Leslie Geer; Ronald S Veazey; Robin J Shattock; Per Johan Klasse; Mark Mitchnick; Laurie Goldman; Lara A Doyle; Brendan C O Muldoon; A David Woolfson; John P Moore; R Karl Malcolm Journal: J Control Release Date: 2011-08-12 Impact factor: 9.776