Dendrimer-based nano artesunate/β-glucan as a promising antimalarial candidate: insights from in vivo evaluations

Abstract

Introduction

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.

Methods

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.

Findings

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 h. 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.

Conclusion

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.