A novel paclitaxel-loaded poly(epsilon-caprolactone)/Poloxamer 188 blend nanoparticle overcoming multidrug resistance for cancer treatment.
A novel paclitaxel-loaded poly(epsilon-caprolactone)/Poloxamer 188 blend nanoparticle overcoming multidrug resistance for cancer treatment.
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DOI：
10.1016/j.actbio.2009.11.035
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发表时间：
2010-06
影响因子：
9.7
通讯作者：
Yangqing Zhang;L. Tang;Leilei Sun;Junbo Bao;Cunxian Song;Laiqiang Huang;Kexin Liu;Yan Tian
中科院分区：
文献类型：
--
作者：
Yangqing Zhang;L. Tang;Leilei Sun;Junbo Bao;Cunxian Song;Laiqiang Huang;Kexin Liu;Yan Tian
肿瘤细胞的多药耐药（MDR）是肿瘤化疗成功的主要障碍。泊洛沙姆已用于癌症治疗以克服MDR。本研究的目的是测试紫杉醇负载的聚（ε-己内酯）/泊洛沙姆188（PCL/泊洛沙姆188）纳米粒克服紫杉醇耐药的人乳腺癌细胞系中的MDR的可行性。分别以市售聚己内酯和自行合成的聚己内酯/泊洛沙姆188复合物为原料，采用水-丙酮溶剂置换法制备紫杉醇纳米粒。PCL/泊洛沙姆188纳米颗粒被发现是球形的形状，往往具有粗糙和多孔的表面。纳米颗粒的平均尺寸约为220 nm，具有窄的尺寸分布。两种纳米粒制剂的体外药物释放曲线均显示出明显的双相释放模式。与PCL纳米颗粒相比，PCL/泊洛沙姆188纳米颗粒（PPNP）在紫杉醇耐药的人乳腺癌细胞系MCF-7/TAX中的摄取水平增加。在MCF-7/TAX细胞培养物中，PCL纳米颗粒的细胞毒性高于商业Taxol®，但差异不显著。然而，PCL/泊洛沙姆188纳米颗粒实现了比PCL纳米颗粒制剂和Taxol®两者显著更高水平的细胞毒性，表明负载紫杉醇的PCL/泊洛沙姆188纳米颗粒可以克服人乳腺癌细胞中的MDR，因此可以具有相当大的乳腺癌治疗潜力。
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(ε-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®, 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.