Abstract

Malaria caused by Plasmodium falciparum remains one of the most pressing public health challenges in sub-Saharan 
Africa and Southeast Asia. Artemisinin-based combination therapies (ACTs) have reduced mortality substantially 
over the past two decades, yet partial artemisinin resistance has emerged, threatening long-term control. 
Pharmacokinetic limitations of conventional antimalarials, such as rapid metabolism and short plasma half-life, 
create subtherapeutic exposure windows that accelerate resistance selection. Nanoparticle drug delivery systems are 
being explored to enhance pharmacokinetics, improve efficacy, and suppress resistance emergence. This review 
evaluates nanoparticle-based antimalarial formulations in comparison with conventional therapies, with emphasis on 
resistance suppression in P. falciparum, particularly in translational and clinical studies. This review synthesizes peer
reviewed studies retrieved from PubMed, Scopus, and Web of Science, focusing on in vitro, in vivo, pharmacokinetic, 
and clinical evidence related to nanoparticle-formulated artemisinin derivatives and partner drugs. Nanoparticle 
systems, including liposomes, polymeric nanoparticles, and solid lipid nanoparticles, extend systemic drug exposure 
by 2–5 fold, increase half-life by up to fourfold, and enhance bioavailability compared with free drug formulations. 
Preclinical studies show nanoparticle-encapsulated dihydroartemisinin lowers IC50 values against resistant P. 
falciparum strains by 30–70%. Clinical pilot data suggest faster parasite clearance, reduced recrudescence, and 
delayed resistance emergence. Sustained drug exposure narrows the pharmacological “selection window,” reducing 
survival of resistant parasites. Conclusion: Nanoparticle-based antimalarials outperform conventional therapies in 
prolonging systemic exposure and suppressing resistance, though large-scale randomized trials, cost-effectiveness 
evaluations, and regulatory frameworks remain necessary before widespread adoption. 
Keywords: Malaria, Plasmodium falciparum, Nanoparticles, Antimalarial therapy, Resistance suppression