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 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.
Method: The artemether-lumefantrine co-loaded NLCs were prepared using
the lipid matrix (5% w/w) (containing beeswax and Phospholipon\uae
90H and Caprol-PGE 860), artemether (0.1%w/w) and lumefantrine
(0.6%w/w), sorbitol (4%w/w), Tween\uae 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\ub4s 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 sustained drug release from the NLC compared with
that seen with chloroquine sulphate and Coartem\uae. Results of
histopathological 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 compliance due to decrease in dosing
frequency as a sustained release formulation