天津医药

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复合载药微球壳聚糖温敏凝胶的初步研究

徐倩1,张旭1,杨小平2,张剑明1,李彦秋1   

  1. 1. 天津医科大学口腔医院
    2. 北京化工大学
  • 收稿日期:2012-07-31 修回日期:2012-12-10 出版日期:2013-04-15 发布日期:2013-04-15
  • 通讯作者: 李彦秋

The Preliminary Study of Temperature-responsive Chitosan Gel Combined with Drug-loaded Chitosan Microspheres

  • Received:2012-07-31 Revised:2012-12-10 Published:2013-04-15 Online:2013-04-15

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摘要：

【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。

关键词: 壳聚糖微球, 壳聚糖温敏凝胶, 药物缓释, 牙周组织工程

Abstract: [Abstract] 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 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..

Key words: Chitosan microspheres, Temperature-responsive chitosan gel, Drug delivery, Periodontal tissue engineering