定量缓释基因重组碱性成纤维细胞生长因子／聚乳酸-聚羟基乙酸植入片的制备及体外释药研究

目的制备基因重组碱性成纤维细胞生长因子／聚乳酸-聚羟基乙酸（rbFGF／PLGA）定量缓释植入片，观察其一般性质、体外释药特性和rbFGF生物活性维持情况。方法溶剂挥发法制备rbFGF／PLGA植入片，用ELISA双抗体夹心法测定植入片中rbFGF含量，进行体外释药试验，检测rbFGF释放速度和含量，并将植入片植入兔下颌牵张成骨区局部缓慢释放观察rbFGF活性。结果rbFGF／PLGA植入片表面光滑平整，质地均匀，rbFGF含量为3.613μg／片。标准曲线方程为C=1280，54A-99.21（n=7，r^2=0.9952），线性范围15.6，1000pg／ml。植入片体外第1天释放rbFGF 10.70％，第9天累积释放51％，第20天释放达到80％以上。兔下颌牵张成骨实验结果显示植入组新骨形成速度和质量均优于对照组。结论rbFGF／PLGA植入片制备工艺良好，植入片中rbFGF生物活性保存良好，具有定量缓释作用并能促进牵张成骨中新骨形成的速度和质量。

Fabrication of sustained release rbFGF/PLGA implanted tablets and release study in vitro

Objective To fabricate sustained release basic fibroblast growth factor/poly lactideco-glycolide （rbFGF/PLGA） implanted tablets and observe their general properties, drug-release characteristics in vitro, and the biologic activity of rbFGF in vivo. Methods The rbFGF/PLGA implanted tablets were fabricate by solvent evaporation method, rbFGF content was determined by double-antibody sandwich ELISA test, drug-release rate and content was detected by during drug-release test in vitro. The tablets was implanted into the rabbit model of mandibular distraction osteogenesis to investigate the biologic activity of rbFGF. Results The surface of rbFGF/PLGA implanted tablets have the feature of smoothness, integrity and uniformity, with a sustained release role in vitro. The content of rbFGF is 3.613 μg per tablet. The equation for the standard curve of the tablet is C = 1280.54A-99.21 （n = 7, r^2=0.9952）, with a linear range between 15.6 - 1000 pg/ml. The in vitro rbFGF release rates of the tablet were 10.70% , 51% and above 80% in the 1st, 9th and 20th day respectively. In the rabbit model of mandibular distraction osteogenesis in which the rbFGF/PLGA tablets were implanted, the formation rate of new bone and the density of bone trabeculae were superior to those of the control group. Conclusions The rbFGF/PLGA implanted tablets have excellent pharmaceutical properties, showing sustained release effect in vitro with good biological activity in vivo. Bone formation and maturation was accelerated during mandibular distraction osteogenesis in rabbits.