Bittner B, Witt C, Mäder K, Kissel T
Department of Pharmaceutics and Biopharmacy, Philipps-University, Katzerbach 63, D-35032, Marburg, Germany.
J Control Release. 1999 Aug 5;60(2-3):297-309. doi: 10.1016/s0168-3659(99)00085-1.
The aim of the present study was to investigate the influence of the chemical insertion of poly(ethylene oxide), PEO, into a poly(lactide-co-glycolide), PLG, backbone on the mechanisms of in vitro degradation and erosion of the polymer. For this purpose microspheres prepared by a modified W/O/W double emulsion technique using ABA triblock copolymers, consisting of PLG A-blocks attached to central PEO B-blocks were compared with microspheres prepared from PLG. Due to their molecular architecture the ABA triblock copolymers differed in their erosion and degradation behavior from PLG. Degradation occurred faster in the ABA polymers by cleavage of ester bonds inside the polymer backbone. Even erosion was shown to start immediately after incubation in different buffer media. By varying pH and ionic strength of the buffer it was found that both mass loss and molecular weight decay were accelerated in alkaline and acidic pH in the case of the ABA triblock copolymers. Although the pH of the medium had a moderate influence on the degradation of PLG, the molecular weight decay was not accompanied by a mass loss during the observation time. In a second set of experiments we prepared bovine serum albumin, BSA, loaded microspheres from both polymers. The release of BSA from ABA microspheres under in vitro conditions parallels the faster swelling and erosion rates. This could be confirmed by electron paramagnetic resonance, EPR, measurements with spin labeled albumin where an influx of buffer medium into the ABA microspheres was already observed within a few minutes. In contrast, PLG microspheres revealed a burst release without any erosion. The current study shows that the environmental conditions affected the degradation and erosion of the pure polymer microspheres in the same way as the release of the model protein. This leads to the conclusion that the more favorable degradation profile of the ABA triblock copolymers was responsible for the improvement of the release profile.
本研究的目的是探究将聚环氧乙烷（PEO）化学插入聚（丙交酯-共-乙交酯）（PLG）主链对聚合物体外降解和侵蚀机制的影响。为此，使用ABA三嵌段共聚物通过改良的W/O/W双乳液技术制备的微球与由PLG制备的微球进行了比较，ABA三嵌段共聚物由连接到中央PEO B嵌段的PLG A嵌段组成。由于其分子结构，ABA三嵌段共聚物的侵蚀和降解行为与PLG不同。ABA聚合物中聚合物主链内的酯键断裂导致降解更快。在不同缓冲介质中孵育后，甚至显示出侵蚀立即开始。通过改变缓冲液的pH值和离子强度发现，对于ABA三嵌段共聚物，在碱性和酸性pH条件下质量损失和分子量衰减均加速。尽管介质的pH值对PLG的降解有适度影响，但在观察期间分子量衰减并未伴随质量损失。在第二组实验中，我们从两种聚合物制备了负载牛血清白蛋白（BSA）的微球。在体外条件下，BSA从ABA微球中的释放与更快的溶胀和侵蚀速率平行。这可以通过用自旋标记白蛋白的电子顺磁共振（EPR）测量得到证实，其中在几分钟内就已经观察到缓冲介质流入ABA微球。相比之下，PLG微球显示出突发释放且没有任何侵蚀。当前研究表明，环境条件对纯聚合物微球降解和侵蚀的影响与模型蛋白的释放方式相同。由此得出结论，ABA三嵌段共聚物更有利的降解特性导致了释放特性的改善。
