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.

中文翻译：

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纳米化姜黄素-苯并噻吩偶联物：治疗脑型疟疾的潜在组合

由于耐药性导致可用抗疟药物的有效性下降，需要继续努力开发新的治疗方法。在这种情况下，联合疗法在开发有效的一线抗疟疗法以降低疟疾死亡率方面具有广阔的前景。本研究探讨了姜黄素纳米化制剂与苯并噻吩化合物 6（3-溴-N-（4-氟苄基）-苯并[b]噻吩-2-甲酰胺）组合的抗疟功效，以期在与单独使用单一疗法相比，剂量非常低。在此，我们在研究中通过 TEM、AFM 和 DLS 分析观察到的尺寸范围为 30-90 nm 的姜黄素和化合物 6（cur-compound 6）的纳米化缀合物。发现纳米化制剂易于分散在水中，物理和化学稳定，并显示姜黄素和化合物 6 的持续释放曲线，直至 48 小时。用纳米化偶联物处理恶性疟原虫寄生虫 24 小时导致寄生虫的快速清除。此外，用纳米化缀合物制剂处理的伯氏疟原虫感染小鼠存活至 90 天，并完全根除红细胞中的寄生虫。由于制剂在水性介质中的分散性增强，因此通过口服给药增加了化合物的吸收，因此纳米化制剂的这种改进的功效是可能的。而且，