尼氟酸结肠靶向小球的制备与体外释药评价

Preparation and in vitro Drug Release Evaluation of Niflumic Acid Colon-targeted Delivery Beads

目的:制备尼氟酸结肠靶向小球,并进行体外释药评价。方法:将尼氟酸包载于D-α-维生素E聚乙二醇1000琥珀酸酯(TPGS1000)中形成纳米胶束,考察尼氟酸纳米胶束的包封率、载药量、粒径、Zeta电位和多分散系数(PDI)。再采用锐孔-凝固法将纳米胶束包裹于低酯果胶中形成尼氟酸结肠靶向小球,观察尼氟酸结肠靶向小球的外观形态,计算其粒径和跨距。比较尼氟酸纳米胶束和尼氟酸结肠靶向小球依次在人工胃液(2 h)、人工小肠液(3 h)和人工结肠液(3 h)中的释药情况。结果:尼氟酸纳米胶束包封率为(93.42±2.33)%、载药量为(8.54±0.36)%(n=3),粒径为(25.8±0.6)nm、Zeta电位为(-18.73±0.23)m V(n=20),PDI为0.25。尼氟酸结肠靶向小球外形圆整,表面纹理粗糙,其粒径为(1.33±0.14)mm(n=3),跨距为0.26。尼氟酸纳米胶束在前5 h内的累积释放度已超过60%,而尼氟酸结肠靶向小球在前5 h内的累积释放度<30%,二者8 h内的累积释放度均>80%。结论:该制备方法简单可行,成功制得具有良好的结肠靶向性能的尼氟酸小球。

OBJECTIVE:To prepare Niflumic acid colon-targeted delivery beads,and to evaluate in vitro drug release.METHODS:Niflumic acid-loaded nanomicelles were prepared with D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS1000)as carrier material.Entrapment efficiency,drug-loading amount,particle size,Zeta potential and polydispersity coefficient(PDI)of Niflumic acid-loaded nanomicelles was investigated.The nanomicelles were encapsulated into pectin by using piercing-solidifying method to form Niflumic acid colon-targeted delivery beads.The morphology of Niflumic acid colon-targeted delivery beads was observed,and particle size and span was calculated.The drug release of Niflumic acid-loaded nanomicelles and Niflumic acid colon-targeted delivery beads in artificial gastric juice(2 h),artificial intestinal fluid(3 h)and artificial colon fluid(3 h)were compared.RESULTS:The encapsulation efficiency of Niflumic acid-loaded nanomicelles was(93.42±2.33)%,drug-loading amount was(8.54±0.36)%;particle size was(25.8±0.6)nm(n=3);Zeta potential was(-18.73±0.23)mV(n=20);PDI was 0.25.Niflumic acid colon-targeted delivery beads were round in appearance and rough in texture;the particle size was(1.33±0.14)mm(n=3)and span was 0.26.Accumulative release rate of Niflumic acid-loaded nanomicelles was more than 60%within first 5 h.Accumulative release rate of Niflumic acid colon-targeted delivery beads was lower than 30%within first 5 h,and accumulative release rate were both higher than 80%in 8 h.CONCLUSIONS:The preparation method is simple and reliable.Niflumic acid colon-targeted delivery beads are prepared successfully.