Evaluation of Pharmacokinetics, Biodistribution, and Antimalarial Efficacy of Artemether-Loaded Polymeric Nanorods.

Artemether oily injection is recommended for the treatment of severe malaria by the intramuscular route. The major limitations of the artemisinin combination therapy are erratic absorption from the injection site and high dosing frequency due to a very short elimination half-life of the drug. Advanced drug delivery systems have shown significant improvement in the current malaria therapy; the desired drug concentration within infected erythrocytes is yet the major challenge. Recently, we have reported the fabrication of artemether-loaded polymeric nanorods for intravenous malaria therapy which was found to be biocompatible with THP-1 monocytes and rat erythrocytes. The objective of the present study was the evaluation of pharmacokinetics, biodistribution, and antimalarial efficacy of artemether-loaded polymeric nanorods. Scanning electron microscopy and confocal microscopy studies revealed that both nanospheres and nanorods were adsorbed onto the surface of rat erythrocytes after an incubation of 10 min. After intravenous administration to rats, artemether nanorods showed higher plasma concentration and lower elimination rate of artemether when compared with nanospheres. The biodistribution studies showed that, at 30 min, the liver concentration of DiR-loaded nanospheres was higher than that of DiR-loaded nanorods after intravenous administration to BALB/c mice. The in vitro schizont inhibition study showed that both nanorods and nanospheres exhibited concentration-dependent parasitic inhibition, wherein at lower concentrations (2 ppm), nanorods were more effective than nanospheres. However, at higher concentrations, nanospheres were found to be more effective. Nanorods showed higher chemosuppression on day 5 and day 7 than nanospheres and free artemether when studied with the Plasmodium berghei mouse model. Moreover, the survival rate of P. berghei infected mice was also found to be higher after treatment with artemether nanoformulations when compared with free artemether. In conclusion, polymeric nanorods could be a promising next-generation delivery system for the treatment of malaria.

Preparation, Standardization and Anti-plasmodial Efficacy of Novel Malaria Nosodes.

BACKGROUND: Resistance to artemisinin and its partner drugs has threatened the sustainability of continuing the global efforts to curb malaria, which urges the need to look for newer therapies to control the disease without any adverse side effects. In the present study, novel homeopathic nosodes were prepared from Plasmodium falciparum and also assessed for their in vitro and in vivo anti-plasmodial activity. METHODS: Three nosodes were prepared from P. falciparum (chloroquine [CQ]-sensitive [3D7] and CQ-resistant [RKL-9] strains) as per the Homeopathic Pharmacopoeia of India, viz. cell-free parasite nosode, infected RBCs nosode, mixture nosode. In vitro anti-malarial activity was assessed by schizont maturation inhibition assay. The in vitro cytotoxicity was evaluated by MTT assay. Knight and Peter's method was used to determine in vivo suppressive activity. Mice were inoculated with P. berghei-infected erythrocytes on day 1 and treatment was initiated on the same day. Biochemical, cytokine and histopathological analyses were carried out using standard methods. RESULTS: In vitro: the nosodes exhibited considerable activity against P. falciparum with maximum 71.42% (3D7) and 68.57% (RKL-9) inhibition by mixture nosode followed by cell-free parasite nosode (62.85% 3D7 and 60% RKL-9) and infected RBCs nosode (60.61% 3D7 and 57.14% RKL-9). The nosodes were non-toxic to RAW macrophage cell line with >70% cell viability. In vivo: Considerable suppressive efficacy was observed in mixture nosode-treated mice, with 0.005 ± 0.001% parasitemia on day 35. Levels of liver and kidney function biomarkers were within the normal range in the mixture nosode-treated groups. Cytokine analysis revealed increased levels of IL-4 and IL-10, whilst a decline in IL-17 and IFN-γ was evident in the mixture nosode-treated mice. CONCLUSION: The mixture nosode exhibited promising anti-malarial activity against P. falciparum and P. berghei. Biochemical and histopathological studies also highlighted the safety of the nosode for the rodent host. The study provides valuable insight into a novel medicament that has potential for use in the treatment of malaria.

Efficacy of Chininum Sulphuricum 30C against Malaria: An in vitro and in vivo Study.

BACKGROUND: New effective, economical and safe antimalarial drugs are urgently needed due to the development of multi-drug-resistant strains of the parasite. Homeopathy uses ultra-diluted doses of various substances to stimulate autoregulatory and self-healing processes to cure various ailments. The aim of the study was to evaluate the in vitro and in vivo antimalarial efficacy of a homeopathic drug, Chininum sulphuricum 30C. METHODS: In vitro antiplasmodial activity was screened against the P. falciparum chloroquine-sensitive (3D7) strain, and cell viability was assessed against normal human dermal fibroblasts and HepG2 cells. Suppressive, preventive and curative studies were carried out against P. berghei-infected mice in vivo. RESULTS: Chininum sulphuricum (30C) revealed good antiplasmodial activity in vitro, with 92.79 ± 6.93% inhibition against the 3D7 strain. The cell viability was 83.6 ± 0.6% against normal human dermal fibroblasts and 95.22 ± 5.1% against HepG2 cells. It also exhibited suppressive efficacy with 95.56% chemosuppression on day 7 with no mortality throughout the follow-up period of 28 days. It also showed preventive activity against the disease. Drug treatment was also safe to the liver and kidney function of the host as evidenced by biochemical studies. CONCLUSION: Chininum sulphuricum 30C exhibited considerable antimalarial activity along with safety to the liver and kidney function of the host.