载胶质源性神经生长因子明胶微球的制备

Preparation of GDNF-loaded gelatin microspheres

目的研究载胶质源性神经生长因子(GDNF)明胶微球的制备。方法采用乳化法制备B型明胶微球,并使用1-乙基-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC)对明胶微球进行交联。通过离子聚合的方式使带相反电荷的B型明胶微球与GDNF结合。对制备的载GDNF明胶微球的形态、粒径分布、溶胀率、交联比率以及体外释放特点进行观察研究。结果制备的明胶微球表面光滑,分散性好,并且成球性良好,平均粒径为(3.91±1.87)μm。可以通过交联剂的浓度和交联的时间控制明胶微球的交联率。在模拟体内环境下,前3d突释现象较明显,3d后GDNF开始呈线性缓慢释放,4-16d每天平均释放83pg。结论 EDC交联的B型明胶微球可以通过离子结合的方式结合GDNF,并能利用载GDNF明胶微球实现GDNF的控释。

Objective To study the preparation of glial cell-derived neurotrophic factor（GDNF）-loaded gelatin microspheres.Methods Type B gelatin microspheres were synthesized by means of emulsion technique,and then cross-linked by EDC.GDNF-loaded microspheres were prepared by a method of complexation occured between positively charged GDNF and negatively charged type B gelatin.The shape,degree of cross-linking,fold swelling ratios,diameter distribution and in vitro release of gelatin microspheres were observed.Results GDNF-loaded gelatin microspheres had smooth surface and good dispersion,which were round with an average diameter of about（3.91±1.87）μm.The cross-linking rate could be modified by different concentrations of EDC and crosslinking times.In vitro release studies with gelatin microspheres exhibited a minimal initial burst release during the first three days.Then the release slowed down in a linear manner（average release of 83 pg GDNF per day for 4-16days）.Conclusion Type B gelatin microsphere cross-linked by EDC can load GDNF via ion complexation.GDNF-loaded gelatin microspheres can be used for locally controlled release of GDNF.