Comparison of the efficacy of free and non-ionic-surfactant vesicular formulations of paromomycin in a murine model of visceral leishmaniasis.
Non-ionic-surfactant vesicular (NIV) formulations of paromomycin have been tested in-vitro and in-vivo for their activity against Leishmania donovani. Production of NIV was dependent both on the surfactant used and on the concentration of paromomycin; only two of the surfactants studied formed vesicles at the highest paromomycin concentration (9 mg mL(-1)). At surfactant-lipid concentrations > or = 1.5 mM, suspensions of NIV (drug- or glucose-loaded) were cytotoxic to macrophages infected with L. donovani; high levels of nitrite were produced in cell supernatants. At surfactant-lipid concentrations < 1.5 mM, drug-loaded NIV were more effective than the same dose of free drug, in terms of the percentage of cells infected and the number of parasites/cell. At surfactant-lipid concentrations < or = 0.15 mM, drug-loaded NIV were ineffective in-vitro. In-vivo, treatment with decaethylene glycol mono n-hexadecyl ether paromomycin NIV was more effective than hexaethylene glycol mono n-hexadecyl ether paromomycin NIV, in terms of suppression of liver and spleen parasite burdens. Against liver parasites, both types of paromomycin-loaded NIV were more effective than free drug. Neither the NIV nor free forms of paromomycin caused significant suppression of bone-marrow parasites. The study shows that entrapment of paromomycin in NIV can be used to increase its antileishmanial activity in-vitro and in-vivo.
Williams
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Department of Immunology, University of Strathclyde, Glasgow, UK.
Mullen
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AB
Baillie
A J
AJ
Carter
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KC
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D005260:Female; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010303:Paromomycin / Q000494:pharmacology / Q000627:therapeutic use*; D013501:Surface-Active Agents / Q000494:pharmacology; D016896:Treatment Outcome
D000981:Antiprotozoal Agents; D013501:Surface-Active Agents; D010303:Paromomycin