NANOPARTICLE-BASED formulation of dihydroartemisinin-lumefantrine duo-drugs: Preclinical Evaluation and enhanced antimalarial efficacy in a mouse model

Artemisinin-based combinations (ACTs) are World Health Organization -recommended treatment for malaria. Artemether (A) and lumefantrine (LUM) were the first co -formulated ACT and firstline treatment for malaria globally, artemether is dihydroartemisinin ' s (DHA ' s) prodrug. Artemisinins and LUM face low aqueous solubility while artemisinin has low bioavailability and short half-life thus requiring continuous dosage to maintain adequate therapeutic drug -plasma concentration. This study aimed at improving ACTs limitations by nano -formulating DHA-LUM using solid lipid nanoparticles (SLNs) as nanocarrier. SLNs were prepared by modified solvent extraction method based on water -in -oil -in -water double emulsion. Mean particle size, polydispersity index and zeta potential were 308.4 nm, 0.29 and -16.0 mV respectively. Nanoencapsulation efficiencies and drug loading of DHA and LUM were 93.9%, 33.7%, 11.9%, and 24.10% respectively. Nanoparticles were spherically shaped and drugs followed Kors-Peppas release model, steadily released for over 72 h. DHA-LUM-SLNs were 31% more efficacious than conventional oral doses in clearing Plasmodium berghei from infected Swiss albino mice.