Preparation, characterization and pre-clinical evaluation of artemether-lumefantrine-paracetamol (AL-P) loaded nanocarriers in the treatment of malaria

Malaria remains a pertinent global health burden. Current artemether-lumefantrine (AL) therapy is limited by low bioavailability and drug resistance, necessitating new approaches. Solid lipid nanoparticles (SLNs) offer a promising delivery system to mitigate these issues. This study investigates SLNs for the co-delivery of AL and paracetamol to enhance the efficacy and safety of this anti-malarial regimen. Solid lipid nanoparticles co-loaded with artemether, lumefantrine, and paracetamol were produced using melt-emulsion ultrasonication and analyzed using dynamic light scattering, transmission electron microscopy, and ultraviolet–visible spectroscopy. Antiplasmodial activity was established in a Plasmodium berghei -infected mouse model using daily dosing and a single 2 mg/kg dose. Parasitemia, survival, and toxicity by histology and biochemistry were quantified. Optimized ALP-SLNs had desirable physicochemical properties, including a particle size of 187.6 ± 3.2 nm, PDI of 0.142, and a zeta potential of − 50.1 ± 1.4 mV, and TEM micrographs confirmed spherical shape. Encapsulation efficiencies were > 88% (ART: 88.79%, LUM: 99.19%, PAR: 99.85%), and loading capacities were ART: 12.4%, LUM: 11.8%, PAR: 13.1%. In vivo antiplasmodial tests for activity against Plasmodium berghei ANKA in Swiss Albino mice exhibited > 95% chemosuppression (95.67%) and 100% day-60 survival with ALP-SLNs, surpassing free drugs and placebo nanoparticles. Toxicity studies in pre-clinical experiments showed normal parameters, except for one mouse that developed a pulmonary lesion. ALP SLNs demonstrated favorable physicochemical properties, a satisfactory safety profile in acute and sub-acute preclinical testing, and superior antiplasmodial efficacy and a highly effective delivery system for malaria triple therapy compared to free drugs. These findings highlight their potential in overcoming malaria treatment challenges, hence supporting further pharmacokinetic and translational studies toward clinical evaluation.