Shimoda J, Onishi H, Machida Y
Department of Clinical Pharmacy, Hoshi University, Tokyo, Japan.
Drug Dev Ind Pharm. 2001 Jul;27(6):567-76. doi: 10.1081/ddc-100105182.
Chitosan (Chi) microspheres were examined in vitro and in vivo in terms of their bioadhesive characteristics to the mucosa of rat small intestine. Chi was labeled with fluorescein isothiocyanate (FITC), and the microspheres (FTC-MS) were prepared by the dry-in-oil method using the obtained fluorescein thiocarbamyl-chitosan (FTC-Chi). FTC-MS with a mean diameter of 27 microm and size distribution of a few micrometers to several tens of micrometers was used for the bioadhesion experiment. FTC-MS exhibited a tendency to adhere to each part of the small intestine to a greater extent than dissolved FTC-Chi, and the ratio of adhering FTC-MS increased as the amount of added FTC-MS decreased. FTC-MS showed slower transit following intraduodenal injection than oral administration. Following the intraduodenal injection of FTC-MS, more than half remained in the upper or middle part of the small intestine for over 8 h. Further, insulin-containing chitosan microspheres with a mean diameter of 20 microm and size distribution of 5 microm to 45 microm were checked in situ for drug absorption, but intraduodenal or intraileal application hardly gave any decrease in plasma glucose level at a very high dose. The present chitosan microsphere system showed good adhesion to the intestinal mucosa, but scarcely facilitated absorption of insulin.
对壳聚糖（Chi）微球在体外和体内对大鼠小肠黏膜的生物黏附特性进行了研究。用异硫氰酸荧光素（FITC）标记壳聚糖，使用得到的荧光硫代氨基甲酰壳聚糖（FTC-Chi）通过油中干燥法制备微球（FTC-MS）。将平均直径为27微米、粒径分布在几微米到几十微米的FTC-MS用于生物黏附实验。FTC-MS比溶解的FTC-Chi更倾向于在小肠各部位大量黏附，并且随着添加的FTC-MS量减少，黏附的FTC-MS比例增加。十二指肠内注射FTC-MS后的转运速度比口服给药慢。十二指肠内注射FTC-MS后，超过一半的微球在小肠上部或中部停留超过8小时。此外，对平均直径为20微米、粒径分布在5微米到45微米的含胰岛素壳聚糖微球进行了原位药物吸收检查，但在非常高的剂量下，十二指肠内或回肠内给药几乎没有使血浆葡萄糖水平降低。目前的壳聚糖微球系统对肠黏膜显示出良好的黏附性，但几乎没有促进胰岛素的吸收。
