Assessment of the activity of atovaquone-loaded nanocapsules in the treatment of acute and chronic murine toxoplasmosis.
The aim of this work was to develop a new pharmaceutical form of atovaquone and to study its activity against Toxoplasma gondii in vitro and in vivo. Nanocapsules were chosen as the oral dosage form of administration. An analytical method was developed to determine the drug content in nanocapsules. The stability of these nanocapsules were assessed by following drug content, size, pH and osmolarity for a period of six months. The in vitro activity of atovaquone-loaded nanocapsules against tachyzoites of T. gondii (RH stain) was comparable to its suspension form. In vivo studies were carried out in murine models of acute and chronic toxoplasmosis. Mice acutely infected with the virulent RH strain were orally treated with a dose regimen of 15 mg/kg/day for 10 days, starting from day 1 post-infection. 75% of the mice receiving atovaquone-loaded nanocapsules survived 30 days post-infection, compared to none of untreated controls and none of mice treated with the suspension with the same dose regimen. In mice chronically infected by the COUL or the ME49 strain (Type II strains), then treated for six weeks, treatment with atovaquone (15 mg/kg/d, nanoparticles or suspension) resulted in a decrease of brain parasitic burden, which was significantly more pronounced in ME49-infected mice and in those treated with drug-loaded nanocapsules. These results show that the sensibility of T. gondii to atovaquone is different according to the strains and that the activity of atovaquone in the treatment of toxoplasmosis is enhanced when administered in nanoparticular form.
Laboratoire de Parasitologie-Mycologie, Hôpital Saint-Louis, Paris, France.
F
F
Sordet
Y
Y
Aumjaud
H
H
Fessi
F
F
Derouin
D000208:Acute Disease; D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D053626:Atovaquone; D001921:Brain / Q000469:parasitology; D002214:Capsules; D002908:Chronic Disease; D003102:Colloids; D004195:Disease Models, Animal; D004337:Drug Carriers; D004355:Drug Stability; D005260:Female; D008168:Lung / Q000469:parasitology; D051379:Mice; D009285:Naphthoquinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D012995:Solubility; D015996:Survival Rate; D013535:Suspensions; D013696:Temperature; D014122:Toxoplasma / Q000187:drug effects / Q000254:growth & development; D014124:Toxoplasmosis, Animal / Q000188:drug therapy* / Q000401:mortality / Q000469:parasitology
D000981:Antiprotozoal Agents; D002214:Capsules; D003102:Colloids; D004337:Drug Carriers; D009285:Naphthoquinones; D013535:Suspensions; D053626:Atovaquone