聚乳酸-聚乙二醇共聚物为载体的缓释疫苗微球的制备及特性研究

 目的制备缓释疫苗微球。方法以聚乳酸-聚乙二醇共聚物(PELA)为载体,醋酸乙酯为有机溶剂,采用W/O/W溶剂扩散法制备PELA疫苗微球。扫描电子显微镜观察微球的形态,激光散射技术测定其粒径分布;聚丙烯酰胺凝胶电泳(SDS- PAGE)研究微球包裹前后疫苗蛋白的稳定性;BCA法测定疫苗微球的载药量和包封率,同时考察疫苗微球的体外释药性能。结果所得微球呈类球形,平均粒径为5.38μm,疫苗微球载药量为5.12%,包封率达75.25%;包裹前后疫苗蛋白的结构稳定; 体外释药结果显示,疫苗微球前3 d以Higuchi方程(r=0.997 7)释放,3 d后则以零级恒速释放(r=0.992 2),28 d累积释药量为69.10%。结论以PELA为载体的疫苗微球具有较高的包封率、载药量和明显的缓释效果。

Preparation and characteristics of PELA-microspheres for vaccine sustained release

OBJECTIVE To prepare the microspheres for vaccine sustained release.METHODS Microspheres containing vaccine were prepared by a modified W/O/W double emulsion-solvent diffusion method with poly-D,L-lactide-co-poly(ethylene glycol) (PELA) as carrier materials and ethyl acetate as organic solvent. Scanning electron microscopy was used for the observation of microspheres. Size distribution was determined by laser scattering technique. The stability of protein was evaluated by SDS-PAGE. The loading capacity and efficiency of vaccine in the microspheres were determined by BCA kits,which was also performed for the release of vaccine from microspheres in vitro.RESULTS Scanning electron micrographs showed that microspheres were almost spherical and the average diameter was about 5.38 μm. The loading capacity and encapsulation efficiency of vaccine in the microspheres was 5.12% and 75.25% , respectively. SDS-PAGE experiment suggested the protein was stable after being incorporated. In vitro release data were described with the following kinetic models: the release profile followed Higuchi equation in 0-3 day(r=0.997 7),the release profile, followed zero-order kinetic in 4-28 day(r=0.992 2). 69.10% Encapsulated vaccine was released over a period of 28 d. CONCLUSION The vaccine-loaded PELA microspheres were found to own a good loading capacity and efficiency,a remarkably sustained release of vaccine.