Preparation, optimization, and evaluation of ligand-tethered atovaquone-proguanil-loaded nanoparticles for malaria treatment.

This work focused on improving antimalarial therapy through the development and characterization of Atovaquone-Proguanil-loaded nanoparticles employing a 32 factorial design. The nanoparticles were prepared from combinations of Poly(lactic-co-glycolic acid) (PLGA) and Eudragit L100 polymers and different concentrations of PVA (polyvinyl alcohol). Based on the results obtained the formulations were characterized for the particle size, zeta potential, encapsulation efficiency, and percent drug release. Among the nine formulations, F5 proved to be the most favorable in the biophysical parameters with a particle size of 176.3 nm, a zeta potential of -33.5 mV, and an encapsulation efficiency of 86% was found in the present investigation. Experimental dissolution profile analysis indicated that F5 had a slow and controlled-release profile where approximately 92.5%. Besides, cytotoxicity studies employing MTT, LDH (lactate dehydrogenase), and Trypan blue reduction test also supported the biocompatibility of nanoparticles and F5 had the highest cell viability (96%) with the least LDH release of 4%. In stability studies conducted for six months, F5 was found to remain stable regarding physicochemical characteristics and drug release profile at different temperature conditions such as room temperature, 4 °C, and 45 °C. The use of folic acid-functionalized nanoparticles is more effective, according to parasitemia, survival rate, and weight loss in mice treated with the nanoparticles. This is because functionalized nanoparticles could be used to enhance anti-malarial therapies.