聚乙二醇-b-聚乳酸末端官能团的合成及在卡巴他赛载药体系中的应用

Poly (ethylene glycol)-b-Poly (lactic acid) Terminal Modification and Application in Cabazitaxel Take Medicine System

为了提高聚乙二醇-b-聚乳酸(PEG-PLA)与药物卡巴他赛(Cabazitaxel)的相容性以及载药能力,对PEG-PLA进行末端官能团改性,一方面通过化学键合的方法,在PEG-PLA末端接枝药物卡巴他赛;另一方面在PEG-PLA的末端实现官能团的修饰,引入苯环(PEG-PLA-Bz)、乙酰基(PEG-PLA-Ac),通过π-π堆叠效应和相似相溶原理来提高PEG-PLA的载药能力。采用核磁共振谱图(1H-NMR)对末端官能化的目标产物进行分析表征,利用高效液相色谱法(HPLC)和药物血浆释放实验测定胶束的包封率、载药量以及在血浆中的药物浓度。结果表明,通过π-π堆叠形成的胶束的包封率最高,可以达到71.5%,相对分子质量分布较均匀,而且药物缓释作用最好,在360 min后血浆中药物的浓度为2.2μg/m L。

To increase the drug-loading capacity and stability of poly（ ethylene glycol）-b-poly（ lactic acid）（ PEG-bPLA）,a terminal modification method was utilized to load cabazitaxel（ CBT）. Effective ways to control drugs release from micelles was conjugating drugs to polymeric materials or cross-linking polymers by chemical reaction or through similar dissolve mutually theory for combination of polymers and drugs. The target product of terminal functionalization was characterized by1 H-NMR. The micelles encapsulation efficiency,drug loading,and drug concentration in plasma were determined by HPLC and drug plasma release assay. In conclusion,the π-π stacking effect introduced by aromatic groups increases the stability and loading capacity of polymeric micelles. The micelles have a drug loading capacity up to71. 5% for CBT. Test the plasma drug concentration,the plasma drug concentration of PEG-PLA-Bz is the best,and the drug concentration in the plasma is 2. 2 μg/m L after 360 min. These results suggest that the micelles based on π-π stacking hold great potential as sustained delivery system.