Nanocarrier based active targeting strategies against erythrocytic stage of malaria.

The Global Technical Strategy for Malaria 2016-2030 aims to achieve a 90% reduction in malaria cases, and strategic planning and execution are crucial for accomplishing this target. This review aims to understand the complex interaction between erythrocytic receptors and parasites and to use this knowledge to actively target the erythrocytic stage of malaria. The review provides insight into the malaria life cycle, which involves various receptors such as glycophorin A, B, C, and D (GPA/B/C/D), complement receptor 1, basigin, semaphorin 7a, Band 3/ GPA, Kx, and heparan sulfate proteoglycan for parasite cellular binding and ingress in the erythrocytic and exo-erythrocytic stages. Synthetic peptides mimicking P. falciparum receptor binding ligands, human serum albumin, chondroitin sulfate, synthetic polymers, and lipids have been utilized as ligands and decorated onto nanocarriers for specific targeting to parasite-infected erythrocytes. The need of the hour for treatment and prophylaxis against malaria is a broadened horizon that includes multiple targeting strategies against the entry, proliferation, and transmission stages of the parasite. Platform technologies with established pre-clinical safety and efficacy should be translated into clinical evaluation and formulation scale-up. Future development should be directed towards nanovaccines as proactive tools against malaria infection.

Long-acting parenteral drug delivery systems for the treatment of chronic diseases.

The management of chronic conditions often requires patients to take daily medication for an extended duration. However, the need for daily dosing can lead to nonadherence to the therapy, which can result in the recurrence of the disease. Long-acting parenteral drug delivery systems have the potential to improve the treatment of chronic conditions. These systems use various technologies, such as oil-based injectables, PLGA-based microspheres, and in situ forming gel-based depots, to deliver different types of drugs. The use of long-acting parenteral formulations for the treatment of chronic infections such as HIV/AIDS and tuberculosis is a recent development in the field. Researchers are also exploring the use of long-acting parenteral formulations for the treatment of malaria, with the aim of reducing dosing frequency and improving adherence to treatment. This review discusses various aspects of long-acting formulation development, including the impact of the physicochemical properties of the drug, the type of long-acting formulation, and the route of administration. The clinical significance of long-acting formulations and recent advances in the field, such as long-acting nanoformulations and long-acting products currently in clinical trials, have also been highlighted.

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.

Fabrication and evaluation of artemether loaded polymeric nanorods obtained by mechanical stretching of nanospheres.

The objective of the present study was to prepare and evaluate artemether-loaded poly (lactic-co-glycolic acid) (PLGA) nanorods by mechanical stretching of nanospheres. Artemether-loaded PLGA nanospheres were prepared by the standard nanoprecipitation method. To prepare the nanorods, nanospheres (129 nm) were embedded in polyvinyl alcohol film. The film was stretched by using an in-house fabricated film stretching apparatus in one dimension at the rate of 10 mm/min in acetone or silicon oil. Nanorods were recovered by dissolving the film in Milli-Q-water after stretching. The effect of film thickness (100 µm vs 150 µm), the ratio of lactide to glycolide in PLGA (50:50 vs 75:25), extent of stretching (2x vs 4x), on the aspect ratio of the nanorods was studied. A sustained release of artemether was observed from both nanospheres and nanorods with almost 85% drug release at the end of 72 h. In cytotoxicity study, almost 90% cell viability was found when THP-1 cells were treated with artemether, nanospheres, and nanorods equivalent to 0.001 to 100 µg/mL of artemether. At all the concentrations of artemether, nanorods showed less haemolysis of RBCs than the nanospheres. Artemether-loaded PLGA nanorods could be successfully prepared by the film stretching method for intravenous delivery of antimalarial drugs.