DESIGN AND EVALUATION OF MUCOADHESIVE MICROPARTICULATE DRUG CARRIERS FOR ORAL ADMINISTRATION OF PEPTIDE DRUGS

1.粘附性微球药物载体的设计(1)建立了粘附性聚合物对脂质体或可生物降解纳米粒等微粒性药物载体进行表面修饰的方法。(2)建立了一种评价聚合物粘附性的新方法。结果表明，壳聚糖具有最强的黏附功能，黏附程度与载体颗粒表面壳聚糖量有关。(3)壳聚糖黏附机理为聚合物与黏液聚合物的物理缠结。2.胰岛素包衣壳聚糖脂质体的肠吸收(1)含胰岛素的壳聚糖包衣脂质体可显著降低大鼠血糖水平。给药后低血糖维持在12h以上，说明壳聚糖包被脂质体在大鼠肠道内有粘附性。(2)壳聚糖包被脂质体的粘附性和脂质体对胰岛素酶降解的保护作用是影响胰岛素吸收的重要因素。

1.Design of mucoadhesive microparticulate drug carriers(1) Methods for surface modification of microparticulate drug carriers such as liposomes or bio-degradable nanoparticles with mucoadhesive polymers were established.(2) A new method for evaluating the mucoadhesive property of polymers was developed using the Coulter counter. It was found that chitosan had the highest mucoadhesive function among the polymers tested and the degree of adhesion was dependent on the amount of chitosan on the surface of carrier particles.(3) The mucoadhesive mechanism of chitosan was suggested to be a physical entanglement of the polymer with mucus polymers.2.Enteral absorption of a peptide drug insulin encapsulated in the drug carriers(1) The blood glucose level of rats was found to be significantly decreased after administration of the chitosan coated liposomes containing insulin. The lowered glucose level was maintained for more than 12h after administration of the liposomal insulin, which suggested mucoadhesion of the chitosan coated liposomes in the intestinal tract of the rats.(2) Both mucoadhesive property of chitosan coated liposomes and protective effect of liposomal encapsulation for enzymatic degradation of entrapped insulin are important factors in insulin absorption with oral administration of insulin encapsulated in chitosan coated liposomes.