Therapeutic evaluation of free and nanocapsule-encapsulated atovaquone in the treatment of murine visceral leishmaniasis

• Published in: Annals of tropical medicine and parasitology 2003-04, Vol.97 (3), p.259-268
• Main Authors: Cauchetier, E., Paul, M., Rivollet, D., Fessi, H., Astier, A., Deniau, M.
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Antiprotozoal Agents - administration & dosage; Atovaquone; Biocompatible Materials - administration & dosage; Biological and medical sciences; Capsules; Dose-Response Relationship, Drug; Drug Compounding; Human protozoal diseases; Infectious diseases; Leishmania infantum - drug effects; Leishmaniasis, Visceral - drug therapy; Leishmaniasis, Visceral - parasitology; Leshmaniasis; Life Sciences; Liver - parasitology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Microscopy, Electron; Naphthoquinones - administration & dosage; Parasitic diseases; Pharmacology. Drug treatments; Polyesters - administration & dosage; Protozoal diseases; Tropical medicine
• ISSN: 0003-4983; 1364-8594
• DOI: 10.1179/000349803235001840

The activities of free atovaquone (ATV) and of poly(D,L-lactide) nanocapsules loaded with the drug, in the treatment of mice with visceral leishmaniasis caused by Leishmania infantum, were compared. Each mouse was infected intravenously with 2×10 7 promastigotes, on day 0. On days 15, 17 and 19, most of the infected mice were treated either with free ATV, in a dimethylsulphoxide/cremophor/water mixture, or with the ATV-loaded nanocapsules (at, respectively, 0.2-1.6 and 0.125-1.0 mg ATV/kg, on each treatment day). The rest of the mice were left untreated, as controls. All the mice were killed on day 21 and dissected so that their livers and spleens could be weighed. The liver parasite burdens, evaluated using the Stauber method, indicated that the ATV-loaded nanocapsules were significantly more effective than the free drug. In nanocapsules, for example, a total dose of 3.0 mg ATV/kg reduced liver burdens by 71.3%, whereas treatment with a higher total dose of the free drug (4.8 mg/kg) only cut the number of liver parasites by 34.4%. The dose-response data indicated that livers would have been cleared of parasites if the nanocapsule preparation had been given as three doses each equivalent to 3 mg ATV/kg, whereas the maximum suppression possible with the free drug would have been about 61%, whatever the dose.