布洛芬/sPEG-b-PLLA嵌段共聚物微球的制备及其体外释药的研究
Preparation of ibuprofen/sPEG-b-PLLA copolymer microspheres and its in vitro release properties
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摘要:
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。
Abstract:Biodegradable four-arm star-shaped poly(ethylene glycol)-block-poly(L-lactic acid) copolymer (sPEG-b-PLLA), four-arm star-shaped poly(L-lactic acid) (sPLLA), linearly poly(ethylene glycol)-block-poly(L- lactic acid) copolymer (PEG-b-PLLA) and linearly poly(L-lactic acid) (PLLA) were synthesized from L-lactice acid, pentaerythritol, poly(ethylene glycol) and star-shaped poly(ethylene glycol), using the method of melt polycondensation, and the products were characterized and confirmed by 1H NMR spectroscopy, FT-IR and GPC. Four types of ibuprofen loaded microspheres based on the above four types of polymers, i.e., IBU/PLLA, IBU/sPLLA, IBU/PEG-b-PLLA, and IBU/sPEG-b-PLLA microspheres were prepared using the method of solvent evaporation, and the optimized preparation technology was obtained via orthogonal experiments, and the drug-encapsulating properties and in vitro drug-releasing properties were studied. The results showed that compared with IBU/PLLA and IBU/PEG-b-PLLA microspheres, the drug encapsulate efficiency of IBU/sPLLA and IBU/sPEG-b-PLLA microspheres were higher and the in vitro drug releasing rate slowed down, which mainly due to the faster degradation of sPLLA and sPEG-b-PLLA for the star-shaped structure and the block copolymerization of sPEG. The drug releasing curves of these three types of microspheres could be fit by first-order equation, and the releasing mechanism was non-Fickian diffusing, i.e., the synergetic effect of polymer degradation and drug diffusion.
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