Ghaferi Mohsen, Amari Samar, Mohrir Bhalchandra Vivek, Raza Aun, Shahmabadi Hasan Ebrahimi, Alavi Seyed Ebrahim
Department of Pilot Nanobiotechnology, Pasteur Institute of Iran, Tehran 1316943551, Iran.
Department of Chemical Engineering, Shahrood Branch, Islamic Azad University, Shahrood 36155-163, Iran.
Pharmaceuticals (Basel). 2020 Mar 11;13(3):44. doi: 10.3390/ph13030044.
This study aimed to evaluate the therapeutic efficacy of the cisplatin encapsulated into polybutylcyanoacrylate (PBCA) nanoparticles for the treatment of kidney cancer. The nanoformulation was successfully developed using the miniemulsion polymerization method and characterized in terms of size, size distribution, drug loading and encapsulation efficiencies, drug release behavior, in vitro cytotoxicity effects, in vivo toxicity, and therapeutic effects. Cisplatin-loaded PBCA nanoparticles were confirmed to be in nanoscale with the drug entrapment efficiency of 23% and controlled drug release profile, in which only 9% of the loaded drug was released after 48 h. The nanoparticles caused an increase in the cytotoxicity effects of cisplatin against renal cell adenocarcinoma cells (ACHN) (2.3-fold) and considerably decreased blood urea nitrogen and creatinine concentrations when compared to the standard cisplatin (1.6-fold and 1.5-fold, respectively). The nanoformulation also caused an increase in the therapeutic effects of cisplatin by 1.8-fold, in which a reduction in the mean tumor size was seen (3.5 mm vs. 6.5 mm) when compared to the standard cisplatin receiver rats. Overall, cisplatin-loaded PBCA nanoparticles can be considered as a promising drug candidate for the treatment of kidney cancer due to its potency to reduce the side effects of cisplatin and its toxicity and therapeutic effects on cancer-bearing Wistar rats.
本研究旨在评估包裹于聚氰基丙烯酸丁酯(PBCA)纳米颗粒中的顺铂对肾癌的治疗效果。采用微乳液聚合法成功制备了该纳米制剂,并对其粒径、粒径分布、载药量、包封率、药物释放行为、体外细胞毒性作用、体内毒性及治疗效果进行了表征。载顺铂的PBCA纳米颗粒经确认处于纳米尺度,药物包封率为23%,药物释放具有可控性,48小时后仅释放9%的载药量。与标准顺铂相比,该纳米颗粒使顺铂对肾细胞腺癌细胞(ACHN)的细胞毒性作用增强(2.3倍),并使血尿素氮和肌酐浓度显著降低(分别降低1.6倍和1.5倍)。该纳米制剂还使顺铂的治疗效果提高了1.8倍,与标准顺铂给药组大鼠相比,可见平均肿瘤大小减小(3.5毫米对6.5毫米)。总体而言,载顺铂的PBCA纳米颗粒因其有潜力降低顺铂的副作用及其对荷癌Wistar大鼠的毒性和治疗效果,可被视为一种有前景的肾癌治疗候选药物。