Nano-Formulation and Preclinical Study of Dihydroartemisinin-Lumefantrine Antimalarial Drug

Artemisinin-based combinations (ACTs) are currently recommended by the World Health Organization for the treatment of both complicated and uncomplicated malaria. A mixture of artemisinin and lumefantrine is considered the first-line antimalarial drug in the treatment of uncomplicated malaria. However, antimalarial drugs are presently being faced with some challenges including low aqueous solubility, non-specificity, low bioavailability, increased dose frequency to maintain the drug therapeutic level in the blood plasma, and poor drug release profile. Drug nanoformulation in a suitable drug carrier system has been expansively studied and shown to improve the drug release profile, and drug aqueous solubility, reducing dose frequency which in turn reduces the drug toxicity and enhances drug bioavailability, hence improving drug efficacy. This work was aimed at designing, nano-formulating, and characterizing DHA-LUM double nano-formulated solid lipid nanoparticles (SLNs) (DHA-LUM SLNs) as a potential drug-delivery system. SLNs were prepared by a modified single solvent extraction method based on a water-in-oil-in-water (w/o/w) double emulsion. The mean zeta potential, polydispersity index, and particle size of the DHA-LUM SLNs were 308.4±3.8 nm, 0.29±0.02, and -16.0±1.3 mV respectively. The encapsulation efficiencies of DHA and LUM in the double nano-formulated drug were 93.92±0.47% and 33.65±1.58% respectively while the loading capacities for DHA and LUM were 11.87±0.0% and 24.10±2.88% respectively. DHA and LUM drugs followed the Kors-Peppas drug release model in the in-vitro drug release studies with a steady drug release recorded for over 72 hours. Morphological analysis by scanning electron microscope showed smooth spherical-shaped DHA-LUM-SLNs. The FTIR overlay spectra showed great similarity in the peak bands of the empty and drug-loaded nanoparticles. The drug-loaded nanoparticles showed less pronounced peaks as compared to DHA and LUM-free drugs. This showed a successful nano-formulation process. The nanoformulated DHA-LUM-SLNs were 31% more effective as compared with conventional oral dose tested in Plasmodium berghei-infected Swiss albino mice. This study showed a successful method for double nano-formulation of the antimalarial drug.