Exosome-Drug Conjugates Delivery: a Promising Strategy for Improving the Solubility and Bioavailability of Artesunate

Artesunate (ATS) is considered the most widely employed artemisnin derivative in the treatment of Plasmodium falciparum malaria. However, poor solubility and low bioavailability of ATS limit its further clinical application. Herein, we developed a new strategy based on the exosome-drug conjugation (EDC) using the milk-derived exosomes for ATS delivery. The exosome-ATS conjugates (EACs) which formed via a facile bio-conjugation of ATS to the exosomal surface, have been demonstrated to be able to boost the solubility and bioavailability of ATS. Maximal improvement of 71.4-fold in the solubility of ATS was attained using EACs. The corresponding entrapment efficiency and drug loading capacity were found to be 90.3% and 73.9% for EACs, respectively. Further, in vivo pharmacokinetics study manifested that a nearly 5-fold higher peak plasma concentration (Cmax) of ATS than the free ATS was achieved by oral administration of EACs, leading to maximum 2.6-fold improved bioavailability of ATS. Moreover, EACs displayed a distinct sustained-release profile of maximum 36.2-fold prolonged half-life of ATS via intravenous delivery. We reported that for the first time the administration of EACs could be a potential drug delivery strategy for ameliorating the pharmacokinetic profile of ATS based on our encouraging results and hoped that our work opened up a new avenue for the development of EDC delivery system.