Abstract

 Malaria due to Plasmodium falciparum remains a major cause of morbidity and mortality, with an estimated 249 
million cases and 608 000 deaths reported globally in 2022, and a high burden in sub–Saharan Africa. Artemisinin
based combination therapies (ACTs) are the cornerstone of treatment, but short drug half-lives, suboptimal 
exposure, and emerging artemisinin resistance threaten their long-term efficacy. This review evaluates nanoparticle 
(NP) encapsulated artemisinin derivatives as a strategy to improve antimalarial performance against P. falciparum. 
A narrative search of PubMed, Web of Science, and major organizational reports (WHO and MMV) from 2000 to 
2025 identified primary preclinical studies, clinical reports, and key reviews on artemisinin chemistry, mechanisms, 
nanoparticle delivery systems, pharmacokinetics, and resistance. Evidence indicates that liposomes, polymeric 
nanoparticles, nanostructured lipid carriers, micelles, and inorganic platforms can increase apparent solubility, 
prolong circulation, enhance parasite killing in vitro and in vivo, and allow dose sparing compared with free drug. 
Encapsulation modifies absorption and distribution, supports controlled release, and may enhance drug exposure at 
the parasite niche while reducing off-target toxicity. Experimental models also suggest that higher and more 
sustained intra-parasitic exposure may limit survival of ring-stage-tolerant parasites and delay resistance selection. 
However, safety data are largely preclinical, and manufacturing, regulatory, and cost barriers remain substantial. 
Nanoparticle-encapsulated artemisinin derivatives are a promising adjunct to current ACTs, but rigorous 
translational pharmacology, scalable formulation, and well-designed clinical trials are required before broad 
implementation is feasible.