Novel Nano-Formulation of Artemisinin for Enhanced Bioavailability and Anti-Plasmodial Efficacy: In Vitro and Murine Model Evidence

Artemisinin bioavailability limitations, including rapid first-pass metabolism and short plasma half-life, compromise its therapeutic efficacy in standard formulations, and nanotechnology-based delivery systems offer a potentially transformative approach to overcoming these pharmacokinetic barriers. This doctoral study developed and characterised a novel chitosan-based nanoparticle formulation of artemisinin and evaluated its pharmacokinetics and anti-plasmodial efficacy in vitro and in a murine P. berghei model. Artemisinin-loaded chitosan nanoparticles were synthesised by ionic gelation and characterised for particle size, zeta potential, encapsulation efficiency, and in vitro drug release kinetics. Anti-plasmodial activity was assessed against P. falciparum 3D7 and multidrug-resistant K1 strains in vitro. Pharmacokinetic parameters and parasite suppression rates were evaluated in BALB/c mice using Peters' four-day suppression test. Optimised nanoparticles had a mean diameter of 182 nm, zeta potential of +28.4 mV, and encapsulation efficiency of 84.7 percent. In vitro anti-plasmodial activity showed a 3.6-fold improvement in IC50 against K1 strain compared to free artemisinin. Murine parasite suppression at equivalent doses was 91.3 percent for nanoformulated versus 74.8 percent for free artemisinin. Oral bioavailability was improved by 2.4-fold. These results provide foundational proof-of-concept for chitosan nanoparticle-mediated artemisinin delivery as a strategy for enhancing efficacy against resistant P. falciparum. Keywords: artemisinin, nanoformulation, chitosan nanoparticles, anti-plasmodial activity, drug delivery.