Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China.
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
Int J Mol Sci. 2021 Sep 27;22(19):10407. doi: 10.3390/ijms221910407.
Amphiphilic copolymers with pendant functional groups in polyester segments are widely used in nanomedicine. These enriched functionalities are designed to form covalent conjugates with payloads or provide additional stabilization effects for encapsulated drugs. A general method is successfully developed for the efficient preparation of functional biodegradable PEG-polyester copolymers via click chemistry. Firstly, in the presence of mPEG as initiator, Sn(Oct)-catalyzed ring-opening polymerization of the α-alkynyl functionalized lactone with D,L-lactide or ε-caprolactone afforded linear mPEG-polyesters bearing multiple pendant alkynyl groups. Kinetic studies indicated the formation of random copolymers. Through copper-catalyzed azide-alkyne cycloaddition reaction, various small azido molecules with different functionalities to polyester segments are efficiently grafted. The molecular weights, polydispersities and grafting efficiencies of azido molecules of these copolymers were investigated by NMR and GPC. Secondly, it is demonstrated that the resulting amphiphilic functional copolymers with low CMC values could self-assemble to form nanoparticles in aqueous media. In addition, the in vitro degradation study and cytotoxicity assays indicated the excellent biodegradability and low cytotoxicity of these copolymers. This work provides a general approach toward the preparation of functional PEG-polyester copolymers in a quite efficient way, which may further facilitate the application of functional PEG-polyesters as drug delivery materials.
具有聚酯段侧基官能团的两亲性共聚物在纳米医学中得到了广泛的应用。这些丰富的功能旨在与有效载荷形成共价轭合物，或为封装药物提供额外的稳定作用。通过点击化学，成功地开发了一种通用方法来有效地制备功能性可生物降解的 PEG-聚酯共聚物。首先，在 mPEG 作为引发剂的存在下，Sn(Oct)催化的 α-炔基功能化内酯与 D,L-丙交酯或 ε-己内酯的开环聚合，得到了带有多个侧基炔基的线性 mPEG-聚酯。动力学研究表明形成了无规共聚物。通过铜催化的叠氮-炔基环加成反应，将各种具有不同官能团的小叠氮分子有效地接枝到聚酯段上。通过 NMR 和 GPC 研究了这些共聚物中叠氮分子的分子量、多分散性和接枝效率。其次，证明了具有低 CMC 值的这种两亲性功能共聚物可以在水介质中自组装形成纳米粒子。此外，体外降解研究和细胞毒性试验表明这些共聚物具有优异的生物降解性和低细胞毒性。这项工作提供了一种通用的方法来制备功能性 PEG-聚酯共聚物，这可能进一步促进功能性 PEG-聚酯作为药物传递材料的应用。
