RATIONAL DESIGN AND ADVANCED IN VITRO EVALUATION OF A NOVEL TRIPLE-COMBINATION SOLID LIPID NANOPARTICLES CARRIER FOR SYNCHRONIZED RELEASE IN ANTIMALARIAL THERAPY

Abstract

In Sub-Saharan Africa, where Plasmodium falciparum is the predominant species, malaria continues to be a major cause of morbidity and mortality. Although Artemether Lumefantrine (AL) is the recommended first-line therapy, its clinical performance is constrained by poor aqueous solubility, low oral bioavailability, and mismatched pharmacokinetics. The need for integrated, optimized drug-delivery strategies is further highlighted by the frequent co-administration of paracetamol for fever management. In an effort to improve formulation stability, bioavailability, and achieve synchronized drug release, this study developed and evaluated SLNs co-loaded with artemether, lumefantrine, and paracetamol. AL-P SLNs were fabricated using hot homogenization, probe ultrasonication, and subsequent spray-drying. The nanoparticles were characterized for particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and drug loading. While surface morphology was investigated using scanning electron microscopy (SEM), thermal behavior and crystallinity were evaluated using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). In vitro drug-release studies were performed in phosphate-buffered saline (pH 6.8 with Tween 80), and the release data were fitted to standard kinetic models. The optimized SLNs exhibited a mean particle size of 138 nm, a narrow PDI of 0.1, and a zeta potential of –26 mV. For all three medications, encapsulation efficiencies were higher than 90%. DSC and XRD analyses confirmed drug amorphization, and TEM imaging revealed spherical nanoparticles with smooth surfaces. In vitro release demonstrated staggered yet complementary kinetics: artemether achieved complete release within 36 h, paracetamol within 48 h, and lumefantrine within 72 h. The Korsmeyer–Peppas model provided the best fit for all release profiles. The co-loaded AL-P SLNs displayed favorable physicochemical characteristics and controlled, synchronized drug-release behavior, highlighting their promise as an enhanced oral delivery system for malaria therapy.