Molecular design of outermost surface functionalized thermoresponsive polymeric micelles with biodegradable cores
Molecular design of outermost surface functionalized thermoresponsive polymeric micelles with biodegradable cores
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DOI：
10.1002/pola.23017
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发表时间：
2008-11
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影响因子：
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通讯作者：
J. Akimoto;Masamichi Nakayama;K. Sakai;T. Okano
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文献类型：
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作者：
J. Akimoto;Masamichi Nakayama;K. Sakai;T. Okano
我们通过可逆加成-断裂链转移自由基（RAFT）聚合和开环聚合相结合的方法制备了具有温敏性的聚（N-异丙基丙烯酰胺-co-N，N-二甲基丙烯酰胺）嵌段和可生物降解的聚（D，L-丙交酯）嵌段的结构明确的二嵌段共聚物。以羟基RAFT试剂为引发剂，采用RAFT聚合法合成了α-羟基，ω-二硫代苯甲酸酯温敏聚合物。利用温敏性聚合物中的α-羟基引发D，L-丙交酯开环聚合，制备了可生物降解的嵌段材料。热敏性嵌段的末端二硫代苯甲酸酯（DTBz）基团容易被还原成巯基并与马来酰亚胺（Mal）反应。在水介质中，两嵌段共聚物产物形成表面功能化的温敏胶束。这些聚合物胶束具有22 μg/L的低临界胶束浓度。在胶束的温度响应研究中，疏水DTBz-表面胶束显示出较低临界溶解温度（LCST）的显著移动，比Mal-表面胶束（40.0 °C）低30.7 °C。此外，胶束LCST控制通过改变各自的非均相端官能二嵌段共聚物的本体混合物的比例。在酸性条件下（pH 5.0）的胶束破坏完成5天内，由于水解降解的PLA核心，无论在生理条件下显示出缓慢的破坏速率。此外，我们成功地提高了水溶性的疏水药物，紫杉醇通过纳入胶束核心。© Wiley Periodicals，Inc.聚合物科学杂志A部分：聚合物化学46：7127-7137，2008
We prepared well-defined diblock copolymers of thermoresponsive poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) blocks and biodegradable poly(D,L-lactide) blocks by combination of reversible addition-fragmentation chain transfer radical (RAFT) polymerization and ring-opening polymerization. α-Hydroxyl, ω-dithiobenzoate thermoresponsive polymers were synthesized by RAFT polymerization using hydroxyl RAFT agents. Biodegradable blocks were prepared by ring-opening polymerization of D,L-lactide initiated by α-hydroxyl groups of thermoresponsive polymers, which inhibit the thermal decomposition of ω-dithioester groups. Terminal dithiobenzoate (DTBz) groups of thermoresponsive blocks were easily reduced to thiol groups and reacted with maleimide (Mal). In aqueous media, diblock copolymer products formed surface-functionalized thermoresponsive micelles. These polymeric micelles had a low critical micelle concentration of 22 μg/L. In thermoresponsive studies of the micelles, hydrophobic DTBz-surface micelles demonstrated a significant shift in lower critical solution temperature (LCST) to a lower temperature of 30.7 °C than that for Mal-surface micelles (40.0 °C). In addition, micellar LCST was controlled by changing bulk mixture ratios of respective heterogeneous end-functional diblock copolymers. Micellar disruption at acidic condition (pH 5.0) was completed within 5 days due to hydrolytic degradation of PLA cores, regardless of showing a slow disruption rate at physiological condition. Furthermore, we successfully improved water-solubility of hydrophobic drug, paclitaxel by incorporating into the micellar cores. © Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7127–7137, 2008