Shim Woo Sun, Kim Sung Wan, Lee Doo Sung
Department of Polymer Science & Engineering, Sungkyunkwan University, Suwon, Gyunggi 440-746, Korea.
Biomacromolecules. 2006 Jun;7(6):1935-41. doi: 10.1021/bm0600567.
Novel pH- and temperature-sensitive biodegradable poly(epsilon-caprolactone-co-lactide)-poly(ethylene glycol) (PCLA-PEG) block copolymers were synthesized with oligomeric sulfamethazine (OSM) end groups (OSM-PCLA-PEG-PCLA-OSM). Aqueous solutions of these block copolymers have shown sol-gel transition behavior upon both temperature and pH changes under physiological conditions (37 degrees C, pH 7.4). The sol-gel transition of these block copolymer solutions was fine-tuned by controlling the PEG length, the hydrophobic to hydrophilic block ratio (PCLA/PEG), and the molecular weight of the sulfamethazine oligomer. Since changes in temperature do not induce gel formation in this pH- and temperature-sensitive block copolymer solution, this hydrogel can be employed as an injectable carrier using a long guide catheter into the body. In addition, the pH of the block copolymer solution showed no change following PCLA degradation over 1 month, and no indication of gel collapse was observed on addition of buffer solution. As such, these properties make the OSM-PCLA-PEG-PCLA-OSM hydrogel an ideal candidate for use as an injectable carrier for certain protein-based drugs known to denature in low-pH environments.
合成了具有低聚磺胺二甲嘧啶（OSM）端基（OSM-PCLA-PEG-PCLA-OSM）的新型pH和温度敏感的可生物降解聚（ε-己内酯-共-丙交酯）-聚（乙二醇）（PCLA-PEG）嵌段共聚物。这些嵌段共聚物的水溶液在生理条件（37℃，pH 7.4）下随温度和pH变化均表现出溶胶-凝胶转变行为。通过控制聚乙二醇长度、疏水与亲水嵌段比（PCLA/PEG）以及磺胺二甲嘧啶低聚物的分子量，对这些嵌段共聚物溶液的溶胶-凝胶转变进行了微调。由于在这种pH和温度敏感的嵌段共聚物溶液中温度变化不会诱导凝胶形成，因此这种水凝胶可以通过长引导导管作为可注射载体注入体内。此外，在1个月内PCLA降解后，嵌段共聚物溶液的pH没有变化，加入缓冲溶液后也没有观察到凝胶塌陷的迹象。因此，这些特性使OSM-PCLA-PEG-PCLA-OSM水凝胶成为用作某些已知在低pH环境中会变性的蛋白质类药物的可注射载体的理想候选物。
