寡聚(D-乳酸)和寡聚(L-乳酸)改性的聚(甲基丙烯酸寡聚乙二醇酯)接枝共聚物双亲共网络凝胶的聚乳酸立体络合作用物理交联

Poly (ethylene glycol) (PEG) is a hydrophilic, non - immune - and non - cytotoxic polymer. However, the limited mechanical strength of PEG hydrogel and weak drug gel interaction are limited. Although the POEGMA hydrogel has solved many problems of PEG hydrogel, POEGMA hydrogel has the swelling and interfacial properties of PEG hydrogel, which can not solve the problem of low uptake and rapid release of protein or hydrophobic drugs. In order to solve the problem of low uptake and rapid release of POEGMA based hydrogel proteins or hydrophobic drugs, the project intends to use oligomeric ethylene glycol methylacrylate (OEGMA) and hydroxyethyl methacrylate oligo poly (L-lactic acid) and hydroxyethyl methacrylate oligo poly (D-lactic acid) macromonomers to synthesize biocompatible graft copolymers POEGMA-g-PLLA and POEGMA-g-PDLA. Through the stereocomplexation between POEGMA-g-PLLA and POEGMA-g-PDLA, physical crosslinking amphiphlic conetwork can improve the delivery capacity of POEGMA hydrogel. The resulting amphiphilic conetwork is composed of hydrophilic POEGMA and hydrophobic PLLA and PDLA, PDLA and PLLA significantly alter the physical and chemical properties of POEGMA hydrogels. This material has good biocompatibility and may contribute to their application in the biomedical field. The study revealed the law of the stereocomplexation of the graft copolymer, and a novel method for the physical crosslinking of the oligo(D-lactide) and oligo(L-lactide) modified graft copolymer was established.

聚(乙二醇)(PEG)是一种亲水性，无免疫原性和非细胞毒性的聚合物。然而，PEG水凝胶为有限的机械强度、和弱的药物-凝胶相互作用所限制。虽然聚(甲基丙烯酸寡聚乙二醇酯)(POEGMA)水凝胶解决了许多PEG水凝胶的问题，但POEGMA水凝胶有类似PEG水凝胶的溶胀和界面性质，不可能解决蛋白质或疏水性药物的低摄取快速释放的问题。为解决POEGMA基水凝胶蛋白质或疏水性药物的低摄取快速释放的问题，本项目拟以甲基丙烯酸寡聚乙二醇酯(OEGMA)和甲基丙烯酸羟乙酯寡聚(L-乳酸)和寡聚(D-乳酸)大分子单体合成生物相容的接枝共聚物POEGMA-g-PLLA和POEGMA-g-PDLA，通过他们之间的立体络合作用交联成双亲共网络凝胶，提高POEGMA凝胶给药容量。双亲共网络是由亲水的POEGMA链段和疏水的PLLA和PDLA络合作用构成，研究揭示立体络络合作用的规律，建立构建双亲共网络凝胶的新方法。

通过PLLA/PDLA之间的氢键络合作用制备了双亲共网络凝胶、化学交联和物理交联双交联双亲共网络凝胶，双亲共网络凝胶在药物缓释等生物医学领域有重要应用。研究和制备了寡聚(D-乳酸)和寡聚(L-乳酸)接枝改性的聚(甲基丙烯酸寡聚乙二醇甲醚酯-co-甲基丙烯酸2-(2-甲氧基乙氧基)乙酯)共聚物温敏性双亲共网络凝胶。制备了寡聚(D-乳酸)和寡聚(L-乳酸)接枝改性的聚(甲基丙烯酸寡聚乙二醇酯-co-甲基丙烯酸2-(2-甲氧基乙氧基)乙酯-co-N,N-二乙基氨基甲基丙烯酸乙酯)接枝共聚物温度/pH双重敏感的双亲共网络凝胶。制备了聚乳酸立体络合和乙二醇二甲基丙烯酸酯(EGDMA)化学交联的双亲共网络温度/pH双敏感性双交联水凝胶。利用ROP和ATRP合成温度/还原响应性嵌段共聚物P(MEO2MA-co-OEGMA)-b-PLLA-SS-PLLA-b-P(MEO2 MA-co-OEGMA)及自组装胶束。提出和证明了PLLA/PDLA之间的氢键络合物理交联(X射线衍射表征)，制备了双亲共网络凝胶以及化学交联和聚乳酸立体络合双交联的双亲共网络凝胶。