Curcumin poly D-L lactide nanoparticles demonstrate superior antiplasmodial Efficacy and multi-target binding compared with dihydroartemisinin: Integrative in vivo and in silico analyses

The urgent rise of drug-resistant malaria underscores the need for innovative antimalarial agents with multi-targeting capabilities. Curcumin, a polyphenolic compound derived from turmeric, is known for its extensive pharmacological properties; however, its low bioavailability hinders its clinical application. This study compared the antiplasmodial activity, safety profile, and multitarget binding potential of curcumin and its nanoparticle formulations with those of dihydroartemisinin (DHA). Curcumin nanoparticles were produced using a modified emulsion-solvent evaporation technique and were characterized through Fourier-transform infrared spectroscopy (FTIR) and dynamic light scattering methods. Acute oral toxicity assessments were conducted in mice following the OECD Guideline 423. Swiss albino mice infected with P. berghei NK-65 were treated with varying doses of curcumin, nanocurcumin, DHA, or distilled water. The parasitemia level was evaluated using Giemsa-stained blood smears. Additionally, molecular docking studies were conducted using AutoDock Vina to target key proteins of P. falciparum , with the visualisation of protein-ligand interactions carried out in Discovery Studio. Both curcumin and nanocurcumin exhibited a dose-dependent increase in parasite clearance, significantly surpassing DHA. Notably, nanocurcumin at lower doses achieved over 90% reduction in parasitemia. Acute toxicity evaluation indicated no fatalities or severe adverse effects at doses up to 5000 mg/kg. Curcumin exhibited superior binding affinities and more comprehensive interactions with various parasite targets compared with DHA. Curcumin, especially in its nanoparticle form, displays potent multi-target antiplasmodial activity and a favourable safety profile in mice, outperforming DHA. These findings advocate for the continued development of curcumin-based therapeutic strategies for malaria, particularly against strains exhibiting drug resistance. • Nanocurcumin exhibited greater antiplasmodial activity compared to dihydroartemisinin. • The use of nanoparticles improved the solubility, stability, and sustained release of curcumin. • Curcumin demonstrated stronger binding affinity to multiple malaria targets than dihydroartemisinin. • In vivo studies indicated that nanocurcumin was safe, with no significant toxicity detected.