Lin Wen-Jen, Chang Kai-Ling
School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
J Biomed Mater Res A. 2008 Jun 1;85(3):692-8. doi: 10.1002/jbm.a.31590.
The poly(epsilon-caprolactone)-co-poly(ethylene glycol) (PCL-MPEG) amphiphilic diblock copolymer with molar ratio of epsilon-CL to MPEG 81:1 is synthesized via a ring-opening polymerization without a catalyst. The M(w) and M(n) molecular weights and the polydispersities are 18,000, 11,000 g/mole and 1.55, respectively. The pegylated amphiphilic copolymer forms micelles with a low critical micelle concentration 6.71 x 10(-8) mole/L, and the average particle size of copolymeric micelles is 62.3 +/- 12.9 nm. The degradation behavior of diblock copolymer was studied in rat plasma at 37 degrees C for 90 days. The changes of mass, composition, morphology, molecular weight, and thermal property of PCL-MPEG copolymer were investigated. The decrease of copolymer mass shows two phases with rate constants of 1.91 x 10(-1) day(-1) in the first-phase (1-24 h) and 1.77 x 10(-3) day(-1) in the second-phase (1-90 days). The degradation of labile ester linkage between PCL block and MPEG block accounts for continuous decrease of copolymer mass in plasma. The decrease of EG molar ratio from 1.30 to 0.67 and prominent reduction of enthalpy of fusion of remained copolymer from 116.5 to 85.2 J/g provide evidences of PCL-MPEG chain scission. On the other hand, the presence of partially degraded copolymers in the residuals results in its polydispersity increased from 1.55 to 2.24 at the end of 90 days. Nevertheless, the surface erosion of copolymer makes the molecular weight not quite different from its original value.
通过无催化剂的开环聚合反应合成了ε-己内酯与甲氧基聚乙二醇（MPEG）摩尔比为81:1的聚（ε-己内酯）-聚（乙二醇）（PCL-MPEG）两亲性二嵌段共聚物。其重均分子量（M(w)）、数均分子量（M(n)）和多分散指数分别为18,000、11,000 g/摩尔和1.55。聚乙二醇化两亲共聚物形成临界胶束浓度低至6.71×10⁻⁸摩尔/升的胶束，共聚物胶束的平均粒径为62.3±12.9纳米。在37℃下于大鼠血浆中对二嵌段共聚物的降解行为进行了90天的研究。研究了PCL-MPEG共聚物的质量、组成、形态、分子量和热性能的变化。共聚物质量的下降呈现两个阶段，第一阶段（1 - 24小时）的速率常数为1.91×10⁻¹天⁻¹，第二阶段（1 - 90天）的速率常数为1.77×10⁻³天⁻¹。PCL嵌段与MPEG嵌段之间不稳定酯键的降解导致共聚物在血浆中的质量持续下降。乙二醇摩尔比从1.30降至0.67，以及剩余共聚物的熔融焓从116.5显著降至85.2焦耳/克，为PCL-MPEG链断裂提供了证据。另一方面，残留物中部分降解共聚物的存在导致其多分散指数在90天结束时从1.55增加到2.24。然而，共聚物的表面侵蚀使得分子量与其初始值相差不大。
