Sadhukha Tanmoy, Prabha Swayam
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, 55455, USA.
AAPS PharmSciTech. 2014 Aug;15(4):1029-38. doi: 10.1208/s12249-014-0139-2. Epub 2014 May 16.
Poor cellular uptake contributes to high dose requirement and limited therapeutic efficacy of the platinum-based anticancer drug carboplatin. Delivery systems that can improve the cellular accumulation of carboplatin will, therefore, likely improve its therapeutic potential. The objective of this study was to evaluate nanoparticles composed of the biodegradable polymer, poly(D, L-lactide-co-glycolide), for carboplatin delivery to tumor cells. Carboplatin-loaded nanoparticles were formulated by double emulsion-solvent evaporation technique. Nanoparticles demonstrated sustained release of carboplatin over 7 days. Cellular uptake of carboplatin encapsulated in nanoparticles was several fold higher than that with free carboplatin in A549 (lung) and MA148 (ovarian) tumor cells. In vitro cytotoxicity studies showed that encapsulation of carboplatin in nanoparticles resulted in a remarkable reduction in the IC50 of carboplatin in several cell lines (up to 280-fold in some cells). Confocal microscopic analysis revealed the presence of carboplatin nanoparticles in several cellular compartments including lysosomes, cytoplasm, and the nucleus. These results demonstrate an enhanced cellular uptake of carboplatin through encapsulation in PLGA nanoparticles and suggest that improved therapeutic efficacy and reduced toxicity may be achieved with this approach.
细胞摄取不佳导致铂类抗癌药物卡铂需要高剂量使用且治疗效果有限。因此，能够提高卡铂细胞蓄积量的递送系统可能会提高其治疗潜力。本研究的目的是评估由可生物降解聚合物聚（D，L-丙交酯-共-乙交酯）组成的纳米颗粒用于将卡铂递送至肿瘤细胞的情况。通过复乳溶剂蒸发技术制备了载卡铂纳米颗粒。纳米颗粒显示卡铂在7天内持续释放。纳米颗粒包封的卡铂在A549（肺癌）和MA148（卵巢癌）肿瘤细胞中的细胞摄取量比游离卡铂高几倍。体外细胞毒性研究表明，将卡铂包封在纳米颗粒中导致几种细胞系中卡铂的半数抑制浓度（IC50）显著降低（在某些细胞中高达280倍）。共聚焦显微镜分析显示卡铂纳米颗粒存在于包括溶酶体、细胞质和细胞核在内的几个细胞区室中。这些结果表明，通过包封在聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒中，卡铂的细胞摄取得到增强，并且表明这种方法可能实现提高治疗效果和降低毒性。
