Abstract

Artemisinin derivatives are the backbone of current malaria therapy, yet Plasmodium falciparum resistance threatens 
global control efforts. Poor solubility, short half-life, and suboptimal tissue distribution limit their efficacy. 
Nanoparticle encapsulation offers potential to enhance drug delivery, improve pharmacokinetics, and reduce 
resistance emergence. This review evaluated nanoparticle-encapsulated artemisinin derivatives, comparing efficacy, 
pharmacokinetics, and resistance prevention potential against P. falciparum. Literature was retrieved from PubMed, 
Web of Science, and Scopus 2010-2025 using search terms “artemisinin,” “nanoparticle,” and “Plasmodium 
falciparum,” focusing on comparative preclinical and clinical data. Liposomes, polymeric nanoparticles, solid lipid 
nanoparticles, and nanocrystals have demonstrated improved solubility, prolonged circulation, and enhanced 
bioavailability. Encapsulation consistently increased in vitro and in vivo parasite clearance rates compared to free 
drug, with some formulations achieving extended half-life by two- to threefold. Pharmacokinetic benefits included 
sustained plasma concentrations above minimum inhibitory levels and improved distribution to infected 
erythrocytes. Several studies suggest reduced selection for resistant strains, potentially through sustained exposure 
and complete parasite clearance. Safety profiles are generally favorable, though long-term toxicity and large-scale 
production challenges remain. Nanoparticle-based artemisinin delivery holds promise for optimizing therapeutic 
efficacy and delaying resistance in P. falciparum. Further clinical validation, stability optimization for endemic 
settings, and cost-effective manufacturing are priorities to enable translational impact. 
Keywords: Artemisinin derivatives, Nanoparticle delivery, Plasmodium falciparum, Pharmacokinetics, Resistance 
prevention.