Abstract

Background: β-artemether (BAT) and lumefantrine (LFT) combination therapies are well recognized for the treatment of malaria. However, the current conventional formulations have several drawbacks.

Objective: The study aims to develop novel lipid nanoparticles (LNP) for efficient delivery of BAT and LFT.

Methods: The LNP were prepared by solvent injection method and optimized by the Box-Behnken experimental design to achieve the desired particle size, maximum entrapment efficiency (EE), and percentage drug release. BAT and LFT in rat plasma were estimated by liquid chromatographytandem mass spectrometry (LC-MS/MS).

Results: Freeze-dried LNP comprised of 78.74% (w/w) lipid, 15.74% (w/w) surfactant, 3.93% (w/w) co-surfactant and 1.57% mannitol with respect to the total inactive components. Mean particle size and zeta potential were found to be 140.22 ± 1.36 nm and -35.23 mv, respectively. EE was 80.60 ± 3.85% for BAT and 69.64 ± 2.63% for LFT. The optimized formulation exhibited a biphasic release profile in phosphate buffer (pH 7.2). In vivo study revealed an increased bioavailability of BAT and LFT from dual drug loaded LNP compared to the pure drug solution. Moreover, the tissue distribution study confirmed the high uptake of both the drugs in the liver and spleen.

Conclusion: The study demonstrated the potential use of the developed formulation for oral administration in the treatment of malaria.

Keywords: Malaria, β-artemether, lumefantrine, solubility, bioavailability, pharmacokinetic, stability.