复合载药微球壳聚糖温敏凝胶的初步研究

摘要

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0.6～2.0 g/L,多聚磷酸钠质量浓度在0.5～1.0 g/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,24 h累计释放率仅为16％,而单纯的壳聚糖温敏凝胶24 h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 micro-spheres (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 microspheres were mixed in chitosan/β-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 accomplish the goal of sustained release of the growth factors.