Title:β-Artemether and Lumefantrine Dual Drug Loaded Lipid Nanoparticles:
Physicochemical Characterization, Pharmacokinetic Evaluation and
Biodistribution Study
Volume: 10
Issue: 3
Author(s): Kashif Shakeel, Farhan Jalees Ahmad, Ranjit Kumar Harwansh and Mohammad Akhlaquer Rahman*
Affiliation:
- Department of Pharmaceutics
and Industrial Pharmacy, College of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia
Keywords:
Malaria, β-artemether, lumefantrine, solubility, bioavailability, pharmacokinetic, stability.
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.
