Effects of artesunate-loaded nanoparticles on Plasmodium berghei treatment in a mouse model.

Abstract

Malaria is still one of the most important parasitic diseases with millions of cases reported globally every year. Combination therapies of artemisinin or its derivatives, with a partner drug, are the first-and second-line treatments for malaria. However, recently, artemisinin partial resistance or tolerance has emerged and emphasizes the need for new therapeutic approaches to malaria. For example, the encapsulation of artemisinin and its derivatives within nanoparticles offers a highly promising potential approach to improved therapeutic efficacy. In this study, we investigated the effects of this using artesunate, dihydroartemisinin and artemisinin. These drugs were captured in nanoparticles of zinc-based metal-organic frameworks (MOFs) and tested on Plasmodium berghei clearance in a heavy-parasite-load mouse model. Results showed that the dosage of 16 mg/kg artesunate nanoparticles, with three injections over a 24 hr interval, had a significantly improved effect on parasite clearance and combatting the occurrence of hyperparasitaemia (parasitaemia ≥ 5 %). However, the same dosage regime, over a 12 hr interval, only delayed the occurrence of hyperparasitaemia. Using a 4-injection regime over 24 hr, both 10 mg/kg dihydroartemisinin nanoparticles and artemisinin nanoparticles showed stronger parasite clearance than the control non-encapsulated artemisinin at the same dose. These findings not only pose opportunities for novel malaria therapeutic approaches against hyperparasitaemia but also indicate a bright future for using nanoparticles for drug development in parasitic protozoa.