Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
PK-PD-Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
Mater Sci Eng C Mater Biol Appl. 2014 May 1;38:85-93. doi: 10.1016/j.msec.2014.01.043. Epub 2014 Feb 3.
Cisplatin is one of the most potent anticancer agent used in the treatment of various solid tumors, however, its clinical use is limited due to severe adverse effects including nephrotoxicity. In this investigation cisplatin loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles were developed and characterized for various in vitro characteristics including size distribution, zeta potential, drug loading and release profile. PLGA nanoparticles were successfully developed as investigated using scanning electron microscopy and exhibited average particles size and zeta potential as 284.8 nm and -15.8 mV, respectively. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated an absence of any polymer-drug interactions. Cisplatin nanoparticles exhibited in vitro anticancer activity against A549 cells comparable to that of cisplatin solution. The biodistribution study in mice indicated that the kidney cisplatin level was significantly (p<0.01) lower with cisplatin nanoparticles than cisplatin solution. Following two cycles of cisplatin treatment, a week apart, blood urea nitrogen level was found to be higher in case of cisplatin solution as compared to cisplatin nanoparticles. Further, there was a significant (p<0.01) increase in plasma creatinine level in case of cisplatin solution as compared to cisplatin nanoparticles. Histopathological examination of kidney from cisplatin nanoparticles treated group revealed no kidney damage, however, a sign of nephrotoxicity was observed in the case of cisplatin solution. The results suggest that PLGA nanoparticle based formulation could be a potential option for cisplatin delivery.
顺铂是一种最有效的抗癌药物，用于治疗各种实体瘤，然而，由于严重的不良反应，包括肾毒性，其临床应用受到限制。在这项研究中，我们制备并表征了载顺铂的聚（乳酸-共-乙醇酸）（PLGA）纳米粒用于各种体外特性，包括粒径分布、Zeta 电位、载药量和释放特性。通过扫描电子显微镜研究成功制备了 PLGA 纳米粒，并表现出平均粒径和 Zeta 电位分别为 284.8nm 和-15.8mV。傅里叶变换红外光谱和差示扫描量热法表明不存在任何聚合物-药物相互作用。顺铂纳米粒表现出体外抗 A549 细胞的抗癌活性，与顺铂溶液相当。在小鼠中的体内分布研究表明，与顺铂溶液相比，顺铂纳米粒在肾脏中的顺铂水平显著降低（p<0.01）。在相隔一周的两个顺铂治疗周期后，与顺铂纳米粒相比，顺铂溶液的血液尿素氮水平明显升高。此外，与顺铂纳米粒相比，顺铂溶液的血浆肌酐水平显著升高（p<0.01）。顺铂纳米粒治疗组的肾脏组织病理学检查显示无肾脏损伤，然而，在顺铂溶液的情况下观察到肾毒性的迹象。结果表明，PLGA 纳米粒制剂可能是顺铂递送的一种有前途的选择。
