Dendrimer-Based Nano Artesunate/β-Glucan as a Promising Antimalarial Candidate: Insights from in Vivo Evaluations

Malaria remains a major global health burden, with increasing concerns regarding resistance to conventional antimalarial therapies, including artemisinin derivatives. This study aimed to develop and evaluate a second-generation dendrimer-based nano artesunate/β-glucan formulation designed to combine antiplasmodial activity with potential immunomodulatory effects against malaria.

A nano artesunate/β-glucan nanocomposite was synthesized using a G2 dendrimer platform and characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), drug loading analysis, solubility assessment, and release kinetics. Antimalarial efficacy was evaluated in a murine Plasmodium berghei model using parasitemia monitoring, lactate dehydrogenase (LDH) assays, and survival analysis. Immunomodulatory effects were assessed through macrophage nitric oxide (NO) production and serum interferon-gamma (IFN-γ) levels. Toxicological evaluation included body weight monitoring, erythrocyte morphology and hemolysis assays, liver enzyme analysis, and histopathological examination of hepatic tissues.

The synthesized nanocomposite showed a mean particle size of 157.5 nm, acceptable size distribution (PDI = 0.284), and spherical morphology. Loading into the dendrimer-based nanocomposite improved the aqueous solubility of artesunate and β-glucan by 83% and 27%, respectively, and enabled sustained drug release over 48 hours. In vivo, the nano artesunate/β-glucan formulation at 100 mg/kg and 80 mg/kg, respectively, achieved complete parasite clearance within 4 days, with no recrudescence during the 21 days of follow-up. This effect was accompanied by increased NO and IFN-gamma levels, suggesting possible immune involvement. Compared with free artesunate and chloroquine, the nanocomposite showed lower hepatotoxicity, minimal hemolysis, preserved erythrocyte morphology, and only minor liver histopathological changes.

The dendrimer-based nano artesunate/β-glucan formulation showed potent antiplasmodial activity, improved solubility, sustained release, and a favorable acute safety profile in a murine malaria model. It may represent a promising antimalarial nano formulation, although further mechanistic and long-term safety studies are needed.