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

1.(1)建立了用黏附聚合物对微颗粒药物载体（如脂质体或可生物降解纳米颗粒）进行表面修饰的方法。(2)提出了一种利用Coulter计数器评价聚合物粘接性能的新方法。结果表明，壳聚糖的黏附作用最强，其黏附程度取决于壳聚糖在载体颗粒表面的用量。(3)认为壳聚糖的粘接机理是聚合物与黏液聚合物的物理缠结。(1)经壳聚糖包被的胰岛素脂质体可显著降低大鼠的血糖水平。胰岛素脂质体给药后，大鼠的血糖水平持续降低12小时以上，说明壳聚糖包被脂质体在大鼠肠道内具有黏附作用。(2)壳聚糖包被脂质体的黏附特性和包被脂质体对包裹胰岛素酶降解的保护作用是影响口服壳聚糖包被脂质体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.