College of Science, Northwest A&F University, Yangling, Shaanxi, PR China.
Colloids Surf B Biointerfaces. 2011 Oct 15;87(2):454-63. doi: 10.1016/j.colsurfb.2011.06.009. Epub 2011 Jun 15.
Rice-like polymeric nanoparticles (NPs) composed of a new redox-responsive polymer, poly(ethylene glycol)-b-poly(lactic acid) (MPEG-SS-PLA), were prepared to carry paclitaxel (PTX) for glutathione (GSH)-regulated drug delivery. The PTX-loaded MPEG-SS-PLA NPs were fabricated using an optimized oil-in-water emulsion/solvent evaporation method. The size and morphology of the prepared NPs were characterized by scanning electron microscopy (SEM). The SEM results demonstrate that the NPs were dispersed as individual particles and were rice-shaped. The PTX loading efficiency, in vitro release, and stability of the NPs were analyzed by high-performance liquid chromatography (HPLC). The HPLC results revealed that the NPs released almost 90% PTX within 96 h when GSH presented at intracellular concentrations, whereas only a very small PTX amount was released at plasma GSH levels. The in vitro cytotoxicities of the NPs against A549, MCF-7, and HeLa carcinoma cells were assessed using a standard methyl thiazolyl tetrazoliun (MTT) assay. The MTT assay results show that the NPs caused concentration- and time-dependent changes in cell viability. To investigate the cellular uptake of the PTX-loaded NPs, visual endocytosis assay was performed using the fluorescent dye coumarin-6 as a model drug. The endocytosis assay results reveal rapid penetration and intracellular accumulation of coumarin-6-loaded NPs, as well as rapid coumarin-6 dispersion from the NPs. Overall, these findings establish that the NPs containing the synthesized redox-responsive polymer MPEG-SS-PLA can be used as potential carrier systems for antitumor drug delivery.
由一种新的氧化还原响应聚合物聚乙二醇- b-聚乳酸（MPEG-SS-PLA）组成的类大米聚合物纳米颗粒（NPs）被制备用于携带紫杉醇（PTX）进行谷胱甘肽（GSH）调节的药物递送。PTX 负载的 MPEG-SS-PLA NPs 是使用优化的油包水乳液/溶剂蒸发法制备的。通过扫描电子显微镜（SEM）对制备的 NPs 的尺寸和形态进行了表征。SEM 结果表明，NPs 作为单个颗粒分散并且呈稻穗状。通过高效液相色谱（HPLC）分析了 NPs 的 PTX 载药量、体外释放和稳定性。HPLC 结果表明，当细胞内浓度存在 GSH 时，NPs 在 96 小时内几乎释放了 90％的 PTX，而在血浆 GSH 水平下仅释放了非常小的 PTX 量。通过标准甲基噻唑基四唑（MTT）测定法评估了 NPs 对 A549、MCF-7 和 HeLa 癌细胞的体外细胞毒性。MTT 测定结果表明，NPs 引起细胞活力的浓度和时间依赖性变化。为了研究载有 PTX 的 NPs 的细胞摄取，使用荧光染料香豆素-6 作为模型药物进行了可视化内吞作用测定。内吞作用测定结果表明，香豆素-6 负载的 NPs 具有快速穿透和细胞内积累的作用，并且香豆素-6 从 NPs 中快速分散。总的来说，这些发现表明，含有合成的氧化还原响应性聚合物 MPEG-SS-PLA 的 NPs 可用作抗肿瘤药物递送的潜在载体系统。
