Improved antimalarial activity of caprol-based nanostructured lipid carriers encapsulating artemether-lumefantrine for oral administration

Abstract

Background: Artemether and lumefantrine display low aqueous solubility leading to poor release profile; hence the need for the use of lipid-based systems to improve their oral bioavailability so as to improve their therapeutic efficacy. Aim and objective: The objective of this work was to utilize potentials of nanostructured lipid carriers (NLCs) for im- provement of the oral bioavailability of artemether and lumefantrine combination and to evaluate its efficacy in the treat- ment of malaria. This study reports a method of formulation, characterization and evaluation of the therapeutic efficacies of caprol-based NLC delivery systems with artemether and lumefantrine. Method: The artemether-lumefantrine co-loaded NLCs were prepared using the lipid matrix (5% w/w) (containing beeswax and Phospholipon® 90H and Caprol-PGE 860), artemether (0.1%w/w) and lumefantrine (0.6%w/w), sorbitol (4%w/w), Tween® 80( 2%w/was surfactant) and distilled water (q.s to 100%) by high shear homogenization and evaluated for phys- icochemical performance. The in vivo antimalarial activities of the NLC were tested in chloroquine-sensitive strains of Plasmodium berghei (NK-65) using Peter´s 4-day suppressive protocol in mice and compared with controls. Histopathological studies were also carried out on major organs implicated in malaria. Results: The NLC showed fairly polydispersed nano-sized formulation (z-average:188.6 nm; polydispersity index, PDI=0.462) with no major interaction occurring between the components while the in vivo study showed a gradual but sus- tained drug release from the NLC compared with that seen with chloroquine sulphate and Coartem®. Results of histopatho- logical investigations also revealed more organ damage with the untreated groups than groups treated with the formulations. Conclusion: This study has shown the potential of caprol-based NLCs for significant improvement in oral bioavailability and hence antimalarial activity of poorly soluble artemether and lumefantrine. Importantly, this would improve patient com- pliance due to decrease in dosing frequency as a sustained release formulation. Keywords: Nanostructured lipid carriers; artemether-lumefantrine; malaria; Caprol.