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

Abstract

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. The objective of this work was to utilize potentials of nanostructured lipid carriers (NLCs) for improvement of the oral bioavailability of artemether and lumefantrine combination and to evaluate its efficacy in the treatment 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. 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/w as surfactant) and distilled water (q.s to 100%) by high shear homogenization and evaluated for physicochemical 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. 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 sustained drug release from the NLC compared with that seen with chloroquine sulphate and Coartem®. Results of histopathological investigations also revealed more organ damage with the untreated groups than groups treated with the formulations. 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 compliance due to decrease in dosing frequency as a sustained release formulation.