载紫杉醇PLGA/F68纳米粒逆转多药耐药用于乳腺癌的治疗

Paclitaxel-loaded PLGA/F68 nanoparticles reverse multidrug resistance in breast cancer cells

目的载紫杉醇聚乳酸聚羟基乙酸共聚物(PLGA)/F68纳米粒逆转耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞多药耐药的可行性研究。方法使用超声乳化溶剂挥发法分别制备载紫杉醇PLGA和载紫杉醇PLGA/F68纳米粒(10%),并对载紫杉醇纳米粒进行表征。载紫杉醇纳米粒的体外释放研究使用高效液相色谱进行分析。最后研究载紫杉醇纳米粒在耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞的细胞摄取和细胞毒性(PLGA/F68组、PLGA组和泰素组)。结果纳米粒呈球形,表面粗糙多孔,平均粒径250 nm左右,粒径分布比较窄,体外药物释放呈双相释放模型。载紫杉醇PLGA/F68纳米粒能够被耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞摄取。载紫杉醇PLGA/F68纳米粒比载紫杉醇PLGA纳米粒(P<0.05)和泰素(TaxolR)(P<0.05)有更高的细胞毒性。结论载紫杉醇PLGA/F68纳米粒能够逆转耐紫杉醇人乳腺癌细胞MCF-7/Taxol细胞的多药耐药,药用辅料Pluronic F68在乳腺癌治疗中具有潜在的应用前景。

Objective To study the feasibility of paclitaxel-loaded PLGA/F68 nanoparticles for reversing multidrug resistance（MDR） in paclitaxel-resistance human breast cancer cell line MCF-7/Taxol.Methods Paclitaxel-loaded nanoparticles（10 %） were prepared by oil-in-water emulsion/solvent evaporation technique using biodegradable PLGA with or without addition of Pluronic F68.The nanoparticles were characterized in terms of size and size distribution,morphology and surface charge.The in vitro drug release profile was measured by high performance liquid chromatography（HPLC）.Cell culture studies were used to evaluate cell uptake and cytotoxicity of the nanoparticles（group PLGA/F68,group PLGA and group Taxol）.Results The PLGA/F68 nanoparticles showed spherical shape with a rough and porous surface.The nanoparticles had an average size of around 250 nm with a narrow size distribution.The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern.The results showed that PLGA/F68 nanoparticles were internalized into paclitaxel-resistant human breast cancer cell line,MCF-7/Taxol.PLGA/F68 nanoparticles achieved significantly higher level of cytotoxicity than both PLGA nanoparticles and TaxolR（P 0.05）.Conclusion It is demonstrated that paclitaxel-loaded PLGA/F68 nanoparticles could reverse MDR in human breast cancer MCF-7/Taxol cells,thus Pluronic F68 have considerable potential for treatment of breast cancer.