Toxicological study of the primaquine phosphate loaded chitosan nanoparticles in mice

Primaquine (PQ) shows activity against the late hepatic stages and latent tissue forms of Plasmodium vivax and Plasmodium ovale. However, liver targeted PQ delivery may be useful to minimize the dose-limiting blood toxicities and side-effects of PQ. The prime objective of this study was the preparation of PQ loaded chitosan nanoparticles (PQ-CS-NPs) in order to enhance drug tolerance and to reduce dose frequency. The morphological analysis of the chitosan NPs displayed particle size in the range 287-686 nm, polydispersity index in the range 0.338-0.430 and zeta potential between 9.21 and 22.80 mV which indicated good stability. PQ-CS-NPs exhibited EE and LC as 64.28 ± 1.85% and 33.18 ± 0.975%, respectively. The in vitro drug release (Batch C7) was 97.80 ± 0.65% after 24 h. After intravenous injection of PQ-CS-NPs in mice, the lethal dose of the PQ significantly reduced when compared to that of free PQ solution.