Laboratory of Nanomedicine, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751 023, Orissa, India.
Acta Biomater. 2010 Aug;6(8):3120-31. doi: 10.1016/j.actbio.2010.02.010. Epub 2010 Feb 10.
In the present study the potential of carboplatin-loaded chitosan-alginate nanoparticles (CANPs) for the treatment of retinoblastoma was investigated. The carboplatin-loaded CANPs were approximately 300 nm in size, exhibited a high zeta potential of approximately 36 mV and drug encapsulation of approximately 20 wt.%. The CANPs were further characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry and transmission electron microscopy. In vitro release studies revealed fast release of approximately 25% of the drug during the first 24h, followed by sustained release. CANPs demonstrated greater and sustained antiproliferative activity of the drug in a dose- and time-dependent manner (carboplatin IC(50)=0.56 microg ml(-1), carboplatin-loaded CANPs IC(50)=0.004 microg ml(-1)), as well as an enhanced apoptotic effect as compared with the drug in solution in a retinoblastoma cell line (Y79). The higher cytotoxic effect of CANPs may be due to their greater cellular uptake as compared with native carboplatin. It was also demonstrated that clathrin-mediated endocytosis plays a key role in the internalization of CANPs in the Y79 cell line. In conclusion, biodegradable chitosan nanoparticles could be used as an effective ocular drug delivery system for sustained intracellular delivery of carboplatin for the treatment of retinoblastoma.
在本研究中，研究了载顺铂壳聚糖-海藻酸钠纳米粒（CANPs）治疗视网膜母细胞瘤的潜力。载顺铂 CANPs 的粒径约为 300nm，具有约 36mV 的高 ζ 电位和约 20wt%的药物包封率。通过傅里叶变换红外光谱、差示扫描量热法和透射电子显微镜对 CANPs 进行了进一步的表征。体外释放研究表明，药物在最初的 24 小时内快速释放了约 25%，随后是持续释放。CANPs 以剂量和时间依赖的方式表现出更大和持续的抗增殖活性（顺铂 IC50=0.56μgml-1，载顺铂 CANPs IC50=0.004μgml-1），以及与溶液中的药物相比，在视网膜母细胞瘤细胞系（Y79）中增强的凋亡作用。CANPs 的更高细胞毒性作用可能是由于与天然顺铂相比，它们具有更高的细胞摄取率。还证明网格蛋白介导的内吞作用在 CANPs 在 Y79 细胞系中的内化中起关键作用。总之，可生物降解的壳聚糖纳米粒可用作治疗视网膜母细胞瘤的有效眼内药物传递系统，用于持续的细胞内递送顺铂。
