Dimeric Artesunate Glycerophosphocholine Conjugate Nano- Assemblies as Slow-Release Antimalarials to Overcome Kelch 13 Mutant Artemisinin Resistance

Y Du; C Giannangelo; W He; GJ Shami; W Zhou; T Yang; DJ Creek; C Dogovski; X Li; L Tilley

Journal article

Dimeric Artesunate Glycerophosphocholine Conjugate Nano- Assemblies as Slow-Release Antimalarials to Overcome Kelch 13 Mutant Artemisinin Resistance

Y Du, C Giannangelo, W He, GJ Shami, W Zhou, T Yang, DJ Creek, C Dogovski, X Li, L Tilley

Antimicrobial Agents and Chemotherapy | AMER SOC MICROBIOLOGY | Published : 2022

DOI: 10.1128/aac.02065-21

Abstract

Current best practice for the treatment of malaria relies on short halflife artemisinins that are failing against emerging Kelch 13 mutant parasite strains. Here, we introduce a liposome-like self-assembly of a dimeric artesunate glycerophosphocholine conjugate (dAPC-S) as an amphiphilic prodrug for the short-lived antimalarial drug, dihydroartemisinin (DHA), with enhanced killing of Kelch 13 mutant artemisinin-resistant parasites. Cryo-electron microscopy (cryoEM) images and the dynamic light scattering (DLS) technique show that dAPC-S typically exhibits a multilamellar liposomal structure with a size distribution similar to that of the liposomes generated using thin-film dispersion (dAPC-L..

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University of Melbourne Researchers

Leann Tilley Author

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Grants

Awarded by Australian Research Council

Funding Acknowledgements

We thank the Australian National Health and Medical Research Council for research support. L.T. was supported by an Australian Research Council Laureate Fellowship. X.L. is thankful for the support of a National Science and Technology Major Project for New Drug Development, China (2017ZX09101002-001-004) for R&D of dimeric artesunate glycerophosphocholine conjugate (dAPC). Y.D. received funding from the China Scholarship Council (CSC) Program (201806090185) for a study period at the University of Melbourne.