Dimeric Artesunate Glycerophosphocholine Conjugate Nano-Assemblies as Slow-Release Antimalarials to Overcome Kelch 13 Mutant Artemisinin Resistance
Yawei Du, Carlo Giannangelo, Wei He, Gerald J. Shami, Wenya Zhou, Tuo Yang, Darren J. Creek, Con Dogovski, Xinsong Li, Leann Tilley
Abstract
assay. To better understand the enhanced killing effect, we investigated processes for deactivation of both the assemblies and DHA, including the roles of serum components and trace levels of iron. Analysis of parasite proteostasis pathways revealed that dAPC assemblies exert their activity via the same mechanism as DHA. We conclude that this easily prepared multilamellar liposome-like dAPC-S with long-acting efficacy shows potential for the treatment of severe and artemisinin-resistant malaria.
Topics & Concepts
ArtemisininLiposomeDihydroartemisininArtesunateMutantProdrugChemistryPlasmodium falciparumBiophysicsBiologyBiochemistryMalariaImmunologyGeneHIV Research and TreatmentMalaria Research and ControlHIV/AIDS drug development and treatment