胰岛素壳聚糖纳米粒的制备

Preparation of insulin-loaded chitosan nanoparticles

目的 制备胰岛素壳聚糖纳米粒。方法 采用酶水解和超滤膜分离技术 ,得到不同相对分子质量的壳聚糖 ,由凝胶渗透色谱法测定其相对分子质量 ;采用溶剂扩散法制备纳米粒 ,研究纳米粒的空间结构 ,测定其粒径、表面电位 (zeta电位 )、模型药物胰岛素包封率及体外释放。结果 通过控制酶水解条件 ,经超滤分离得到 3种不同相对分子质量的壳聚糖 ,凝胶渗透色谱法测得的重均相对分子质量 (MW)分别为 10 2 89,4 15 0 0和 10 1870。经溶剂扩散法制备得到的壳聚糖纳米粒 ,呈类圆形球体 ,粒径分布较窄 ,且随制备工艺中乙醇加入量的增加、分散用超声次数的增多 ,以及壳聚糖分子量的降低 ,粒径变小。壳聚糖纳米粒带正电荷 ,zeta电位值大于 +30mV。放射免疫法测得的药物包封率为 72 .6 6 %。在壳聚糖酶存在条件下 ,前 1h体外释放药物较快 ,1h后趋于平稳 ,并能持续释放 6h。结论 选用合适相对分子质量壳聚糖制备胰岛素壳聚糖纳米粒 ,方法简便 ,药物包封率高 。

OBJECTIVE: To prepare insulin-loaded chitosan nanoparticles. METHODS: Chitosan with different molecular weights was prepared by enzymatic degradation and ultrafiltration separation. Their molecular weights were determined by gel permeation chromatography (GPC). Chitosan nanoparticles were prepared by solvent diffusion method. Several characteristics of chitosan nanoparticles such as morphology, particle size, zeta potential, drug entrapment efficiency and drug release in vitro were evaluated. RESULTS: Chitosan with three different molecular weights were obtained by controlling the conditions of enzymatic degradation and ultrafiltration separation. The molecular weights of chitosan determined by gel permeation chromatography (GPC) were 10 289, 41 500, 101 870, respectively. The chitosan nanoparticles prepared by solvent diffusion technique showed a spheric shape and exhibited a narrow particle size distribution, and became smaller after increasing the concentration of alcohol in the system or increasing the sonication treatment times. The distribution of particle size also turned to narrower when using lower molecular weight chitosan. Due to the high zeta potentials of chitosan nanoparticle systems (over + 30 mV), these systems were relatively stable. The average entrapment efficiency of insulin was 72.66% determined by radioimmunoassay. Insulin release from nanoparticles in the delivery vehicle containing chitosanase showed a rapid delivery in the initial hour and then became slow in the next five hours. CONCLUSION: It was easy to prepare the insulin-loaded chitosan nanoparticles with chitosan with optional molecular weights. A high envelopment and certain sustained release effect could be obtained.