Nanoformulation of Artemisinin Derivatives for Enhanced Bioavailability and Targeted Delivery in Cerebral Malaria: An Experimental Pharmacology Study

Cerebral malaria, the most severe neurological manifestation of Plasmodium falciparum infection, carries high mortality and neurological sequelae rates in Nigeria despite available artemisinin-based therapy. Limitations in artemisinin bioavailability, blood-brain barrier penetration, and rapid metabolic clearance constrain treatment efficacy in cerebral malaria. This experimental study developed, characterized, and evaluated novel nanoformulations of dihydroartemisinin for enhanced bioavailability and targeted central nervous system delivery applicable to cerebral malaria management. Polymeric nanoparticles using poly(lactic-co-glycolic acid), solid lipid nanoparticles, and transfersome vesicular systems were fabricated and optimized using response surface methodology. Physicochemical characterization included particle size, zeta potential, drug encapsulation efficiency, and in vitro release profiling. In vitro blood-brain barrier permeation was assessed using a co-culture transwell model. Ex vivo antiplasmodial activity was evaluated against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains. In vivo pharmacokinetic studies were conducted in Wistar rat models. Transfersome-encapsulated dihydroartemisinin demonstrated 3.4-fold improvement in oral bioavailability compared to free drug, with significantly enhanced blood-brain barrier permeation in vitro. Antiplasmodial activity was superior across all resistant strains compared to non-encapsulated drug. Pharmacokinetic modelling confirmed extended half-life and reduced clearance for nanoformulated preparations. These findings establish proof-of-concept for artemisinin nanoformulation as a strategy to improve cerebral malaria treatment outcomes and provide a translational platform for future clinical development of nanoformulated antimalarials in Nigeria. Keywords: nanoformulation, artemisinin, cerebral malaria, bioavailability, blood-brain barrier