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.
Malaria remains a major parasitic disease caused mainly by Plasmodium falciparum and Plasmodium vivax, and drug-resistant parasites continue to challenge disease control. Drug repurposing may help identify compounds with antimalarial potential. Here, we evaluated gallopamil, an L-type calcium channel blocker, using in vitro, ex vivo, in vivo and in silico approaches. Gallopamil inhibited the chloroquine-resistant P. falciparum W2 strain in vitro (IC₅₀ = 3.65 µM) and showed ex vivo activity against clinical isolates of P. falciparum and P. vivax from CEPEM/RO, with median IC₅₀ values of 6.4 and 9.87 µM, respectively. Selectivity indices calculated using HepG2 cytotoxicity data ranged from >51 to >137, indicating in vitro selectivity relative to HepG2 cells. In a preliminary murine P. berghei suppressive assay, gallopamil at 5 mg/kg reduced parasitemia by more than 40% at the day-5 endpoint, as measured by light microscopy and flow cytometry. Stage-specific assays showed that gallopamil inhibited parasite development when treatment began at the ring stage (p < 0.000001), whereas no significant inhibition was observed when treatment started with predominantly schizont-stage parasites (p = 0.30). Molecular docking predicted interactions between gallopamil and residues of Plasmodium hexose transporters, including LYS-51, GLN-167, ASN-309 and ASN-339, with binding energies of -6.1 kcal/mol for PvHT1 and -7.8 kcal/mol for PfHT1. These findings support gallopamil as an early antiplasmodial hit compound and provide a transporter-related mechanistic hypothesis for future functional validation.
