Molecular Sciences Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
IUBMB Life. 2020 Dec;72(12):2637-2650. doi: 10.1002/iub.2394. Epub 2020 Oct 9.
The declining effectiveness of the available antimalarial drugs due to drug resistance requires a continued effort to develop new therapeutic approaches. In this context, combination therapies hold a great promise for developing effective first-line antimalarial treatments for reducing malaria mortality. The present study explores the antimalarial efficacy of nanotized formulation of curcumin in combination with benzothiophene compound 6 (3-bromo-N-(4-fluorobenzyl)-benzo[b]thiophene-2-carboxamide) with a view to achieve better efficacy at a very low dose in comparison to that accomplished with monotherapy alone. Herein, we formulated nanotized conjugate of curcumin and compound 6 (cur-compound 6) in the size range of 30-90 nm as observed via TEM, AFM and DLS analysis in the study. The nanotized preparation was found to be readily dispersible in water, physically and chemically stable and exhibited sustained release profile of both curcumin and compound 6 till 48 hr. Treatment of P. falciparum parasites with the nanotized conjugate for 24 hr resulted in rapid clearance of the parasites. Furthermore, P. berghei infected mice treated with nanotized conjugate formulation survived till 90 days with complete eradication of the parasites from RBC. This improved efficacy of the nanotized formulation was possible because of the increased absorption of the compounds via oral administration owing to enhanced dispersibility of the formulation in aqueous medium. Moreover, an improved oral bioavailability of the nanotized formulation lowered the dosage at which the pharmacological effect was achieved while avoiding any observable adverse harmful side effects.
由于耐药性的存在，现有的抗疟药物效果逐渐下降，因此需要继续努力开发新的治疗方法。在这种情况下，联合疗法为开发有效的一线抗疟治疗方法以降低疟疾死亡率提供了很大的希望。本研究探讨了纳米化姜黄素与苯并噻吩化合物 6（3-溴-N-（4-氟苄基）-苯并[b]噻吩-2-甲酰胺）联合的抗疟疗效，以期在非常低的剂量下实现比单独使用单一药物更好的疗效。在此，我们通过 TEM、AFM 和 DLS 分析观察到，将纳米化姜黄素和化合物 6 （姜黄素-化合物 6）制成 30-90nm 的纳米级共轭物。研究发现，纳米化制剂在水中易于分散，物理和化学性质稳定，并表现出姜黄素和化合物 6 的持续释放特性，直至 48 小时。用纳米化共轭物处理恶性疟原虫寄生虫 24 小时后，寄生虫迅速清除。此外，用纳米化制剂处理感染伯氏疟原虫的小鼠直至 90 天，寄生虫从 RBC 中完全消除。这种纳米化制剂的疗效提高是因为由于制剂在水性介质中的分散性增强，从而增加了化合物的吸收，使得通过口服给药能够提高化合物的吸收。此外，纳米化制剂的口服生物利用度提高降低了实现药理作用所需的剂量，同时避免了任何可观察到的有害副作用。
