眼用妥布霉素羧甲基壳聚糖微球的制备及体外释放性能研究

Preparation and in vitro release properties of tobramycin-loaded carboxymethyl chitosan microspheres for ophthalmology

目的制备眼用妥布霉素羧甲基壳聚糖微球,并评价其体外释药性能。方法采用乳化-交联固化法制备妥布霉素羧甲基壳聚糖微球,并以微球的收率、粒径分布和包封率作为评价指标,使用Box-Behnken实验设计优化得到妥布霉素羧甲基壳聚糖微球的最优处方。通过马尔文激光粒度仪测定了微球的粒径分布,扫描电镜观察其微观结构,考察微球在人工泪液中的释药性能。结果优化得到微球的处方组成:羧甲基壳聚糖质量浓度为3.5%,甲醛质量浓度为1.5%,Span-80质量浓度为0.8%;妥布霉素羧甲基壳聚糖微球的平均粒径为(12.3±0.4)μm,呈圆整球状分布,无聚集;体外释药前期较快,后期较为缓慢,药物释放符合Higuchi释药模型。结论通过使用Box-Behnken实验设计优化制备得到妥布霉素羧甲基壳聚糖微球,制备工艺简易,重现性良好,具有较好的缓释性能,可进一步进行实验研究。

Objective To prepare tobramycin-loaded carboxymethyl chitosan microspheres(Tob-loaded CMCMs)for ophthalmology and evaluate their in vitro release properties.Methods The Tob-loaded CMCMs were prepared by emulsification-crosslinking curing method.The yield,particle size distribution and encapsulation efficiency of microspheres were used as evaluation indexes.The BoxBehnken experimental design was used to obtain the optimal formulation of the Tob-loaded CMCMs.The particle size distribution of the Tob-loaded CMCMs was measured by Malvern laser particle size analyzer.The microstructure was observed by scanning electron microscopy.The in vitro release properties of the microspheres were investigated in artificial tears.Results The optimal formulation of the Tob-loaded CMCMs was optimized as followed:The carboxymethyl chitosan concentration was 3.5%,the formaldehyde concentration was 1.5%,the Span-80 surfactant concentration was 0.8%.The average particle size of Tob-loaded CMCMs was(12.3±0.4)μm,which had a regular spherical distribution and no aggregation.In vitro release was faster in the early stage and slower in the later stage,which was consistent with the Higuchi model.Conclusion The formulation of Tob-loaded CMCMs was optimized by Box-Behnken experimental design.The preparation process was simple,and the reproducibility was good.The Tob-loaded CMCMs could delay drug release,which laid the experimental foundation for animal experiments.