Khodaverdi Elham, Tayarani-Najaran Zahra, Minbashi Elham, Alibolandi Mona, Hosseini Javad, Sepahi Samaneh, Kamali Hossein, Hadizadeh Farzin
Iran J Pharm Res. 2019 Winter;18(1):142-155.
Microwave irradiation was used to synthesize poly (caprolactone)-poly (ethylene glycol) (PEG-PCL) and poly (lactic acid)-poly (ethylene glycol) (PEG-PLA) copolymers that are composed of biodegradable polymers including PEG, PLA, and PCL. These copolymers were used for loading docetaxel in nanoparticles. Single emulsion-solvent evaporation technique was applied for preparing the PEG-PLA and PEG-PCL mixed nanoparticles (micelles and polymersomes) with different proportions, including 0:1, 1:1, 3:1, 1:3, and 1:0. The unimodal gel permeation chromatography curve showed low polydispersity of the di-block copolymers. The drug release curves of formulations were compared. Micelles and polymersomes of 75% PEG-PCL and 25% PEG-PLA (P5 and M5) have the lowest burst release (5%) at the same period compared to the other copolymers. The dynamic light scattering and TEM results clarified that the size and shape of the formulations are uniform. The cytotoxicity effect of P5 and M5 was evaluated in different cell lines. The best one was found to P5 with half maximal inhibitory concentration (IC) between 1.48-11.79 µg/mL. The pro-apoptotic effect of P5 was confirmed with flow cytometry study. These mixed micelles (M5) and polymersomes (P5) was found to be superior formulations than non-mixed ones.
采用微波辐射合成了由聚乙二醇（PEG）、聚乳酸（PLA）和聚己内酯（PCL）等可生物降解聚合物组成的聚（己内酯）-聚（乙二醇）（PEG-PCL）和聚（乳酸）-聚（乙二醇）（PEG-PLA）共聚物。这些共聚物用于在纳米颗粒中负载多西他赛。采用单乳液溶剂蒸发技术制备了不同比例（包括0:1、1:1、3:1、1:3和1:0）的PEG-PLA和PEG-PCL混合纳米颗粒（胶束和多囊泡体）。单峰凝胶渗透色谱曲线表明二嵌段共聚物的多分散性较低。比较了制剂的药物释放曲线。与其他共聚物相比，75%PEG-PCL和25%PEG-PLA（P5和M5）的胶束和多囊泡体在同一时期的突释率最低（5%）。动态光散射和透射电镜结果表明制剂的尺寸和形状均匀。评估了P5和M5在不同细胞系中的细胞毒性作用。发现最佳的是P5，其半数最大抑制浓度（IC）在1.48-11.79µg/mL之间。通过流式细胞术研究证实了P5的促凋亡作用。发现这些混合胶束（M5）和多囊泡体（P5）比未混合的制剂更优。
