可降解聚乙交酯-丙交酯缓释微球用于甲状旁腺相关肽的持续释放  

Biodegradable PLGA Microspheres for Controlled Delivery of Parathyroid Hormone Related Peptide

作　　者：张士博[1] 张喆[2] 于美娜[1] 刘童斌[1] 王晶晶[1] 蔡青[1] 陈莉[2] 贺超良[3] 孟维艳[1] 陈学思[3] 

机构地区：[1]吉林大学口腔医学院,长春130021 [2]东北师范大学化学学院,长春130024 [3]中国科学院长春应用化学研究所生态环境高分子材料重点实验室,长春130022

出　　处：《高分子学报》2014年第2期270-275,共6页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号50973108,51003103,21174142);科技部国际合作与交流专项(项目号2010DFB50890);吉林省科技发展计划(项目号201101082,20110332);吉林省卫生厅科研课题(课题号2012Z087)资助项目

摘　　要：采用水包油包水(W1/O/W2)复乳溶剂挥发法制备了包载甲状旁腺激素相关肽(PTHrP)的聚乙交酯-丙交酯(PLGA)微球,通过核磁,红外,GPC,扫描电子显微镜等观察PLGA载药微球的结构,表明载药微球具有良好的球形结构,其平均粒径约为8μm.而体外模拟释放表明,此PLGA载药微球能实现PTHrP1-34长达25天的持续释放.并通过MTT法、碱性磷酸酶活性测定等检测负载PTHrP1-34的PLGA微球缓释系统对小鼠成骨细胞MC3T3-E1增殖及分化的影响,结果表明PTHrP1-34浓度为1×10-9mol/L时对MC3T3-E1增殖促进效应最大,且随着药物作用时间的延长,缓释系统促进细胞增殖、分化的作用越明显.PLGA microspheres were chosen as the carrier to overcome the limitations of application for parathyroid hormone related peptide （PTHrP） which can increase the number and viability of osteoblasts and promote bone formation with a low-dose, long time, intermittent administration. PLGA microspheres were prepared by a water-in-oil-in-water （W1/O/W2） double emulsion solvent evaporation and PTHrP1-34 was encapsulated to the microspheres by a technique with good sphericity and high efficiency. The micrographs of polyester microspheres were evaluated by scanning electron microscope （SEM）. The polyester microspheres had a good spherical shape. PTHrP1-34 loaded microspheres exhibited a slow release behavior for about 25 days,which was accord with expection. The effect of PTHrP1-34 loaded microspheres on pre-osteoblastic proliferation was studied via cell proliferation evaluation experiments. The results demonstrated that PTHrP1-34 loaded PLGA microspheres can enhance the proliferation and differentiation of MC3T3 cell effectively. Alkaline phosphatase （ALP） quantification experiment was also performed to investigate the influence of differentiation. The cells incubated with PTHrP1-34 loaded PLGA microspheres exhibited higher ALP level which was related to the differentiation. In summary, PTHrP1-34 loaded PLGA microspheres show great potential as a promising delivering and releasing carriers for application of oral implantology.

关 键 词：甲状旁腺相关肽 聚乙交酯 丙交酯 微球 控制释放 

分 类 号：TQ460.1[化学工程—制药化工]