Biodegradable long circulating cellular carrier for antimalarial drug pyrimethamine

The objective of the present study was to develop targeted engineered nanoerythrosomes based intravenous formulation of antimalarial drug pyrimethamine.

The nanoerythrosomes formulation was developed by sonication method and optimized for effective drug loading at variable drug concentration, surface morphology, viscosity and sedimentation volume.

The in vitro drug release of formulated product was found to be delayed after 8 hours, having good stability at 4 ± 1°C and showing controlled in vivo release. Tissue distribution studies showed higher accumulation of drug in the liver (18.71 ± 1.4 μg/ml) (P < 0.05) at 1 hour in case of pyrimethamine-loaded nanoerythrosomes as compared to that in free drug (12.82 ± 0.7 μg/ml). Higher amount of drug, i.e. 14.18 ± 0.9 μg/ml (P < 0.05), was found after 24 hours in the liver in case of pyrimethamine-loaded nanoerythrosomes as compared to free drug concentration of 9.72 ± 0.5 μg/ml).

Data showed that developed pyrimethamine-loaded nanoerythrosomes hold promise for targeting and controlling the release of drug and for improving treatment of malaria when they are combined with rapid acting antimalarials such as artemisinin.

A decrease in the concentration of pyrimethamine in kidneys and lungs after 24 hours was observed as compared to that observed after 1 hour, showing no or little involvement of these organs in the clearance of drug-loaded nanoerythrosomes.