Artesunate-quercetin/luteolin dual drug nanofacilitated synergistic treatment for malaria: A plausible approach to overcome artemisinin combination therapy resistance

Malaria is one of the major global health challenge with 300 million new cases annually. The best regimen for treating Plasmodium falciparum induced malaria is based on artemisinin and its derivatives which were prescribed as artemisinin combination therapy (ACT). These are highly effective drugs resulting in rapid clearance of parasites even in severe P. falciparum induced malaria patients. However, from the past few years parasites resistant to ACT's have begun to emerge in various parts of the world such as Cambodia and Greater Mekong Subregion. Currently, the ACT's resistance is comparatively low with clinical presentation of hindered artemisinin clearance and a small reduction in artemisinin sensitivity in cultured isolates. In order to counteract this, we hypothesize artesunate and quercetin/luteolin loaded self-nanoemulsifying drug delivery system (SNEDDS) which could provide an alternate drug combination to ACT induced P. falciparum resistance to treat malaria. The proposed formulation design can significantly help in reduction of dose and dosing frequency, which ultimately enhance patient compliance with decreased drug toxicity. We presume that if this hypothesis proves correct, it may become an additional novel tool and one of the plausible therapeutic options in treating malaria.