Jain Shubham, Meka Sai Rama Krishna, Chatterjee Kaushik
Department of Materials Engineering, Indian Institute of Science, Bangalore 560012, India.
ACS Biomater Sci Eng. 2016 Aug 8;2(8):1376-1385. doi: 10.1021/acsbiomaterials.6b00297. Epub 2016 Jul 25.
The objective of this study was to engineer a biodegradable polymeric system for sustained release of piperine for cancer treatment. We prepared nanofibrous patches of poly(ε-caprolactone) (PCL) and gelatin (GEL) blends of different ratios by electrospinning. The PCL/GEL nanofibers were loaded with up to 30 wt % piperine, a phytochemical derived from black pepper, which is believed to exhibit anticancer, antiarthritis, antibacterial, antioxidant, and anti-inflammatory properties. Scanning electron microscopy revealed that the fiber diameter was in the range of 300-400 nm. Fourier-transform infrared spectroscopy confirmed that the drug was successfully loaded into the nanofiber mats. In vitro release kinetics revealed the sustained release of the drug with 50% release in 3 days from the PCL/GEL (50:50 by weight) blend fibers. The reduced viability and growth of HeLa and MCF-7 cancer cells on the piperine eluting nanofibers demonstrated anticancer activity in vitro. The proliferation of noncancerous cells such as NIH3T3 cells and human mesenchymal stem cells was affected to a markedly lesser extent. Flow cytometry revealed that the released piperine induced the generation of reactive oxygen species (ROS) and cell cycle arrest in the G2/M phase, leading to cell death of cancer cells. The findings of this study suggest that piperine-loaded nanofiber mats could be developed into implantable biodegradable patches for use in postsurgical cancer treatment.
本研究的目的是设计一种用于持续释放胡椒碱以治疗癌症的可生物降解聚合物系统。我们通过静电纺丝制备了不同比例的聚（ε-己内酯）（PCL）和明胶（GEL）共混物的纳米纤维贴片。PCL/GEL纳米纤维中负载了高达30 wt%的胡椒碱，胡椒碱是一种源自黑胡椒的植物化学物质，据信具有抗癌、抗关节炎、抗菌、抗氧化和抗炎特性。扫描电子显微镜显示纤维直径在300 - 400 nm范围内。傅里叶变换红外光谱证实药物已成功负载到纳米纤维垫中。体外释放动力学表明药物具有持续释放特性，从PCL/GEL（重量比50:50）共混纤维中3天释放50%。在胡椒碱洗脱纳米纤维上，HeLa和MCF - 7癌细胞的活力和生长降低，证明了其体外抗癌活性。非癌细胞如NIH3T3细胞和人间充质干细胞的增殖受到的影响明显较小。流式细胞术显示释放的胡椒碱诱导活性氧（ROS）的产生并使细胞周期停滞在G2/M期，导致癌细胞死亡。本研究结果表明，负载胡椒碱的纳米纤维垫可开发成可植入的可生物降解贴片，用于癌症术后治疗。
