Improved anti-malarial parasite efficacy with heparin-artemisinin nanoemulsions

Artemisinin and its derivatives have been widely applied as the most effective drugs in the treatment of malaria since their introduction in the last century. However, challenges such as short half-life, limited bioavailability, and increasing drug resistance have prompted researchers to explore new strategies in the development of antimalarial drugs. In this study, a nano-targeting drug delivery system (HEP@ART@NEs) is developed consisted of heparin as the outer shell and artemisinin in the inner core, utilizing a high-pressure homogenization approach. The specific targeting effect of HEP@ART@NEs is achieved through surface multivalent interactions between heparin with both Plasmodium falciparum merozoites as well as the surface of infected red blood cells (iRBCs). The physical and chemical properties of HEP@ART@NEs, as well as its anti-malarial activity both in vitro and in vivo, are systematically investigated. HEP@ART@NEs demonstrate enhanced antimalarial effects, delay malaria recrudescence, and improve survivability in a rodent model with P. berghei ANKA infection compared to the treatment with conventional artemisinin treatment. Overall, this study indicates that HEP@ART@NEs hold promise as a platform for a rational design of targeted delivery of antimalarial drugs.