The activity and ultrastructural localization of primaquine-loaded poly (d,l-lactide) nanoparticles in Leishmania donovani infected mice.
The activity of primaquine (PQ) was compared to that of PQ-loaded Poly (D,L-Lactide) (PLA) nanoparticles against Leishmania donovani. The association of PQ with PLA nanoparticles increased the antileishmanial in vitro and in vivo effects of intravenously administered drug while its toxicity was reduced. The effectiveness of PQ-loaded PLA nanoparticles was 3.3 times as high as that of free drug in the suppression of amastigotes in the liver of BALB/c mice. A total dose of 30 mg PQ bound/kg (600 mg PLA/kg) was well tolerated and no sign of acute toxicity was observed. A similar dose of free drug resulted in 15% weight loss. No significant leishmanicidal activity was observed for unloaded PLA nanoparticles. Ultrastructural studies showed the uptake of drug-loaded nanoparticles by Leishmania-infected Kupffer cells. Nanoparticles were identified closed to amastigotes.
Rodrigues
J M
JM
Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté de Pharmacie, Chatenay-Malabry, France.
Croft
S L
SL
Fessi
H
H
Bories
C
C
Devissaguet
J P
JP
D000818:Animals; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005260:Female; D066298:In Vitro Techniques; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D011319:Primaquine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011319:Primaquine