Qian Haitao, Wohl Adam R, Crow Jordan T, Macosko Christopher W, Hoye Thomas R
Departments of Chemistry and Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455.
Macromolecules. 2011 Sep 27;44(18):7132-7140. doi: 10.1021/ma201169z.
Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable copolymer that is also acceptable for use in a variety of biomedical applications. Typically, a random PLGA polymer is synthesized in a bulk batch polymerization using a tin-based catalyst at high temperatures. This methodology results in relatively broad polydispersity indexes (PDIs) due to transesterification, and the polymer product is often discolored. We report here the use of 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU), a known, effective, and convenient organocatalyst for the ring-opening polymerization of cyclic esters, to synthesize random copolymers of lactide and glycolide. The polymerization kinetics of the homo- and copolymerizations of lactide and glycolide were explored via NMR spectroscopy. A novel strategy that employs a controlled addition of the more reactive glycolide monomer to a solution containing the lactide monomer, the poly(ethylene glycol) (PEG) macroinitiator, and DBU catalyst was developed. Using this tactic (semi-batch polymerization), we synthesized a series of block copolymers that exhibited excellent correlation of the expected and observed molecular weights and possessed narrow PDIs. We also measured the thermal properties of these block copolymers and observed trends based on the composition of the block copolymer. We also explored the need for experimental rigor in several aspects of the preparations and have identified a set of convenient reaction conditions that provide polymer products that retain the aforementioned desirable characteristics. These polymerizations proceed rapidly at room temperature and without the need for tin-based catalysts to provide PEG-b-PLGAs suitable for use in biomedical investigations.
聚乳酸-乙醇酸共聚物（PLGA）是一种可生物降解的共聚物，在各种生物医学应用中也可接受使用。通常，无规PLGA聚合物是在高温下使用锡基催化剂通过本体间歇聚合合成的。由于酯交换反应，这种方法导致多分散指数（PDI）相对较宽，并且聚合物产物常常变色。我们在此报告使用1,8-二氮杂双环[5.4.0]-十一碳-7-烯（DBU），一种已知的、有效且方便的用于环状酯开环聚合的有机催化剂，来合成丙交酯和乙交酯的无规共聚物。通过核磁共振光谱探索了丙交酯和乙交酯的均聚和共聚反应动力学。开发了一种新颖的策略，即向含有丙交酯单体、聚乙二醇（PEG）大分子引发剂和DBU催化剂的溶液中控制添加反应性更高的乙交酯单体。使用这种策略（半间歇聚合），我们合成了一系列嵌段共聚物，这些共聚物的预期分子量与观察到的分子量具有极好的相关性，并且具有窄的PDI。我们还测量了这些嵌段共聚物的热性能，并根据嵌段共聚物的组成观察到了趋势。我们还在制备的几个方面探索了实验严谨性的必要性，并确定了一组方便的反应条件，这些条件可提供保留上述理想特性的聚合物产物。这些聚合反应在室温下快速进行，无需锡基催化剂即可提供适用于生物医学研究的PEG-b-PLGA。
