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 as sociation of PQ with PLA nanoparticles increased the antileishmanial i n vitro and in vivo effects of intravenously administered drug while i ts toxicity was reduced. The effectiveness of PQ-loaded PLA nanopartic les was 3.3 times as high as that of free drug in the suppression of a mastigotes 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 w as observed. A similar dose of free drug resulted in 15% weight loss. No significant leishmanicidal activity was observed for unloaded PLA n anoparticles. Ultrastructural studies showed the uptake of drug-loaded nanoparticles by Leishmania-infected Kupffer cells. Nanoparticles wer e identified closed to amastigotes.