Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, People's Republic of China.
Acta Biomater. 2010 Jun;6(6):2045-52. doi: 10.1016/j.actbio.2009.11.035. Epub 2009 Dec 5.
Multidrug resistance (MDR) of tumor cells is a major obstacle to the success of cancer chemotherapy. Poloxamers have been used in cancer therapy to overcome MDR. The objective of this research is to test the feasibility of paclitaxel-loaded poly(epsilon-caprolactone)/Poloxamer 188 (PCL/Poloxamer 188) nanoparticles to overcome MDR in a paclitaxel-resistant human breast cancer cell line. Paclitaxel-loaded nanoparticles were prepared by a water-acetone solvent displacement method using commercial PCL and self-synthesized PCL/Poloxamer 188 compound, respectively. PCL/Poloxamer 188 nanoparticles were found to be of spherical shape and tended to have a rough and porous surface. The nanoparticles had an average size of around 220nm, with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a clear biphasic release pattern. There was an increased level of uptake of PCL/Poloxamer 188 nanoparticles (PPNP) in the paclitaxel-resistant human breast cancer cell line MCF-7/TAX, in comparison with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxol in the MCF-7/TAX cell culture, but the differences were not significant. However, the PCL/Poloxamer 188 nanoparticles achieved a significantly higher level of cytotoxicity than both of PCL nanoparticle formulation and Taxol(R), indicating that paclitaxel-loaded PCL/Poloxamer 188 nanoparticles could overcome MDR in human breast cancer cells and therefore could have considerable therapeutic potential for breast cancer.
多药耐药（MDR）肿瘤细胞是癌症化疗成功的主要障碍。泊洛沙姆已被用于癌症治疗以克服 MDR。本研究旨在测试载紫杉醇的聚（ε-己内酯）/泊洛沙姆 188（PCL/Poloxamer 188）纳米粒克服紫杉醇耐药的人乳腺癌细胞系中 MDR 的可行性。分别采用商业 PCL 和自制 PCL/Poloxamer 188 化合物，通过水-丙酮溶剂置换法制备载紫杉醇纳米粒。PCL/Poloxamer 188 纳米粒呈球形，表面粗糙多孔。纳米粒的平均粒径约为 220nm，粒径分布较窄。两种纳米粒制剂的体外药物释放曲线均呈明显的两相释放模式。与 PCL 纳米粒相比，紫杉醇耐药的人乳腺癌细胞系 MCF-7/TAX 中 PCL/Poloxamer 188 纳米粒（PPNP）的摄取水平增加。在 MCF-7/TAX 细胞培养中，PCL 纳米粒的细胞毒性高于商业紫杉醇，但差异无统计学意义。然而，PCL/Poloxamer 188 纳米粒的细胞毒性明显高于 PCL 纳米粒制剂和 Taxol(R)，表明载紫杉醇的 PCL/Poloxamer 188 纳米粒可克服人乳腺癌细胞中的 MDR，因此对乳腺癌具有相当大的治疗潜力。
