复合载药微球壳聚糖温敏凝胶的初步研究

The Preliminary Study of Temperature-Responsive Chitosan Gel Combined withDrug-Loaded Chitosan Microspheres

目的制备复合载药微球壳聚糖温敏凝胶(T-responsive CG/CMS),观察其对牛血清蛋白的缓释效果,为负载外源性生长因子应用于牙周组织再生提供参考。方法以牛血清蛋白为模型药物,利用离子凝胶法制备的牛血清蛋白壳聚糖微球,用扫描电镜观察其表面形态,测定药物载药量及包封率。并将牛血清蛋白壳聚糖微球共混于壳聚糖/β-甘油磷酸钠温敏凝胶体系形成T-responsive CG/CMS-BSA,并利用紫外分光光度计检测其对牛血清蛋白的缓释效果。结果壳聚糖质量浓度在0.6～2.0g/L,多聚磷酸钠质量浓度在0.5～1.0g/L时均可生成形态较好,粒径均匀的壳聚糖微球。利用优化配方制备T-responsive CG/CMS在体温37℃发生溶胶到凝胶的转变,具有良好的温敏性能。体外释放试验表明T-responsive CG/CMS对牛血清蛋白的释放速度明显减慢,24h累计释放率仅为16%,而单纯的壳聚糖温敏凝胶24h累计释放率高达70%。结论 T-responsive CG/CMS对蛋白类药物具有良好的缓释作用,有望应用于牙周组织工程中生长因子的缓释。

Objective To prepare temperature-responsive chitosan gel combined with drug-loaded chitosan microspheres （T-responsive CG/CMS）, and to investigate its controlled-release effect to provide a reference for the load of exogenous growth factors used in periodontal tissue regeneration. Methods The bovine serum albumin （BSA） was used as the model drug. The BSA-loaded microspheres were prepared using ionic gelation method. The surface morphology was observed by scanning electron microscopy. The drug loading and encapsulation efficiency were determined. Then the BSA-loaded mi crospheres were mixed in chitosan/-glycerophosphate system to form T-responsive CG/CMS-BSA. The sustained-release effect of bovine serum albumin was detected by ultraviolet sepectrophotometry. Results The good shape and uniform particle size citosan microsphere（CSM）was generated when chitosan concentration was between 0.6 g/L and 2.0 g/L, tripolyphosphate concentration was between 0.5 g/L and 1.0 g/L. With optimizing the formulation of T-responsive CG/CMS, its transition from sol to gel occurred at 37 ℃, showing the temperature sensitivity. The release in vitro tests showed that the BSA release rate of the T-responsive CG/CMS slowed down, and the 24 h cumulative release rate was only 16%, while the 24 h cumulative release rate of the unmingled temperature-responsive chitosan gel was up to 70%. Conclusion T-responsive CG/CMS showed the potential for sustained release of protein-based drugs, and thus it could be used in periodontal tissue engineering to ac complish the goal of sustained release of the growth factors.