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以L-乳酸、季戊四醇、聚乙二醇和星型聚乙二醇为原料,采用直接熔融缩聚法分别合成了线形聚L-乳酸(PLLA)、四臂星型聚L-乳酸(sPLLA)、线形聚乙二醇-聚L-乳酸嵌段共聚物(PEG-b-PLLA)和四臂星型聚乙二醇-聚L-乳酸嵌段共聚物(sPEG-b-PLLA),并用FT-IR、凝胶渗透色谱(GPC)和1H NMR确认了产物的结构。以上述4种聚合物为基材,布洛芬(IBU)为模型药物,采用溶剂挥发法制备了IBU/PLLA载药微球、IBU/sPLLA载药微球、IBU/PEG-b-PLLA载药微球和IBU/sPEG-b-PLLA载药微球,采用正交试验设计对载药工艺进行优化,研究了具有不同结构和组成、以聚乳酸为基础的系列可降解聚合物的载药特性及其载药微球的体外释药特性。结果显示,与IBU/PLLA及IBU/PEG-b-PLLA相比,IBU/sPLLA和IBU/sPEG-b-PLLA微球的药物包封率略高;聚乳酸的星型化以及与星型聚乙二醇进行嵌段聚合,均促进了聚合物基体的溶蚀,有利于改善载药微球的早期突释,使药物的释放更为平稳;4种载药微球的释药曲线均符合一级方程,其释药机制为non-Fickian扩散,即药物扩散和聚合物骨架降解的协同作用。
L-lactic acid, pentaerythritol, polyethylene glycol and star polyethylene glycol were synthesized by direct melt polycondensation. Linear PLLA, sPLLA, Polyethylene glycol-poly-L-lactic acid block copolymer (PEG-b-PLLA) and four arm star polyethylene glycol-poly L-lactic acid block copolymer (sPEG-b-PLLA) , Gel permeation chromatography (GPC) and 1H NMR confirmed the structure of the product. IBU / PLLA drug loaded microspheres, IBU / sPLLA drug loaded microspheres and IBU / PEG-b-PLLA were prepared by solvent evaporation method using the above four kinds of polymers as the substrate and ibuprofen as the model drug Drug-loaded microspheres and IBU / sPEG-b-PLLA drug-loaded microspheres. The orthogonal design was used to optimize the drug loading process. A series of biodegradable polymers with different structures and compositions, based on polylactic acid Characteristics and drug release microspheres in vitro release characteristics. The results showed that the drug encapsulation efficiency of IBU / sPLLA and IBU / sPEG-b-PLLA microspheres was slightly higher than that of IBU / PLLA and IBU / PEG-b-PLLA; The block polymerization of ethylene glycol promoted the corrosion of the polymer matrix and improved the early burst release of the drug-loaded microspheres, which made the drug release more stable. The release curves of the four drug-loaded microspheres were consistent with Level equation, the release mechanism of non-Fickian diffusion, that the drug diffusion and degradation of the polymer skeleton synergies.