Artesunate drug-loaded 2D nano-shuttle landing on RBCs infected with malaria parasites

Artesunic acid (AS⁰), a derivative of artemisinin, is recommended for the treatment of severe and complicated malaria, but its use is limited because of limitations such as a short half-life, non-specific targeting capability, low bioavailability, etc. To overcome these issues, a novel 2D inorganic delivery shuttle system for an AS⁰ drug to target the malarial host, red blood cells (RBCs), is explored by immobilizing AS⁰ into 2D metal hydroxides to form AS^- (artesunate, the deprotonated form of artesunic acid) nanohybrid drugs. Haemolysis assay showed that the AS^- nanohybrids not only are haemo-compatible but also target RBCs due to the electrostatic interaction and hydrogen bonding between RBCs and AS^- nanohybrids. As clearly demonstrated by the subsequent parasite lactate dehydrogenase assay, the antimalarial effect of the AS^- nanohybrids is determined to be 6 times more effective than that of intact AS⁰ against malaria. Therefore, the AS^- nanohybrids with haemo-compatible 2D inorganic carriers could be the promising drug delivery systems for targeting the malarial host, RBCs.