课题背景：四川大学生物力学实验室在国家自然科学基金项目(29970747)的资助下,完成了bFGF微球制备过程的优化以及相关的细胞实验和动物实验。在此基础上,国家自然科学基金项目(30100190)资助本实验室体外模拟膝关节的压力环境,考察微球在静压力下降解的情况。

应用要点：近年来由于聚乳酸类高分子聚合物良好的生物相容性,其作为缓释药物载体的研究越来越受到重视,可以利用此类材料的降解特性和化学构成特点,制备可控制的,靶向性治疗的缓释微球。当药物缓释微球应用于膝关节这样的关节腔时,必然考虑关节腔内压力对微球降解的影响。

偏倚或不足：本实验设计压力装置,在实验过程中压力值保持恒定不变。而实际膝关节内的压力,随着人体姿势的不同和屈膝角度的不同发生很大的变化。因而,可以在接下来的工作中设计人工膝关节,将bFGF-PLGA缓释微球注入其中,考察在人工膝关节模拟人体膝关节运动过程中的降解情况,可以更加全面的考察膝关节内部的物理因素(包括应力因素)对药物微球的影响。

摘要
目的：体外模拟膝关节腔的静压力环境,观察静压力是否对碱性成纤维生长因子-聚乳酸-羟基乙酸(bFGF-PLGA)缓释微球的降解规律产生影响。
方法：实验于2006-06/2007-05在四川大学生物力学实验室完成。①实验材料：采用复乳法制作bFGF-PLGA缓释微球，冷冻离心，干燥后保存备用。自行研制压力加载装置，分别可以提供0.065 MPa和5.0 MPa的大气压力，保压效果良好。②实验方法：将微球分为0.065 MPa实验组，5.0 MPa实验组和常压对照组进行实验。37 ℃恒温下，以磷酸盐缓冲液作为缓释微球降解和释药介质，分析静压力对bFGF-PLGA缓释微球降解规律的影响。
结果：①0.065 MPa和5.0 MPa实验组, bFGF-PLGA缓释微球未发生突然性的变形破裂，微球表面光滑，球形良好。②0.065 MPa实验组与常压对照组体外聚合物重均分子质下降和质量丧失趋势一致。③5.0 MPa实验组与常压对照组相比，聚合物重均分子质量下降、质量丧失均加快。
结论：静压力对bFGF-PLGA缓释微球体外降解的各项指标产生较大影响,以5.0 MPa的静压力下效果最明显。bFGF-PLGA缓释微球在临床上直接用于膝关节腔给药时,必须考虑关节腔压力值的影响。
关键词：静压力；缓释微球；降解；碱性成纤维细胞生长因子；聚乳酸-聚羟基乙酸共聚物；生物材料

李萍，段宏，邹远文.静压力对碱性成纤维生长因子-聚乳酸-羟基乙酸缓释微球降解的影响[J].中国组织工程研究与临床康复，2008，12(10):1819-1822 [www.zglckf.com/zglckf/ejournal/upfiles/08-10/10k-1819(ps).pdf]

Effect of static pressure on degradation of basic fibroblast growth factor-polylactic-co-glycolic acid controlled release microspheres

Abstract

AIM：To simulate static pressure environment of knee joint cavity in vitro, observe the effect of static pressure on the degradation of basic fibroblast growth factor-polylactic-co-glycolic acid (bFGF-PLGA) controlled release microsphere (MS).
METHODS: The experiment was performed at the biomechanics laboratory, Sichuan University from June 2006 to May 2007.①The bFGF-PLGA MS was prepared by double emulsion method, then frozen, centrifuged, and dried for using. The self-made compressive instruments was used to maintain the static pressure of 0.065 MPa and 5.0 MPa, separately.②MS were divided into 0.065 MPa experimental group, 5.0 MPa experimental group and normal pressure (control) group. At the constant temperature of 37 ℃, phosphate buffer solution was used as the medium of degradation and release, then the effect of static pressure on the degradation of bFGF-PLGA MS was analyzed.
RESULTS: ①Under static pressure of 0.065 MPa and 5.0 MPa, the sudden rupture of MS was not found, with even and smooth surface of MS.②Under the pressure of 0.065 MPa, the trend of molecular weight (Mw) loss and quality loss of the polymer was consistent with the control group in vitro.③Compared with the control group, the rate of Mw loss and quality loss were obviously quicker under the pressure of 5.0 MPa.
CONCLUSION: Static pressure has a conspicuous influence on the indicators of degradation in vitro of bFGF-PLGA controlled release MS, especially at the pressure of 5.0 MPa. Once bFGF-PLGA MS is injected into the knee joint cavity, the pressure of joint cavity should be considered cautiously.

Li P, Duan H, Zou YW.Effect of static pressure on degradation characteristics of basic fibroblast growth factor-polylactic-co-glycolic acid controlled release microspheres.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(10):1819-1822(China) [www.zglckf.com/zglckf/ejournal/upfiles/08-10/10k-1819(ps).pdf]