Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes
Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes
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DOI：
10.1023/a:1016009313548
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发表时间：
1996-06-01
影响因子：
3.7
通讯作者：
Kawashima, Y
中科院分区：
文献类型：
--
作者：
Takeuchi, H;Yamamoto, H;Kawashima, Y
目的.评价聚合物包覆脂质体的粘膜粘附性，以开发用于口服吸收不良药物（如肽类药物）的新型药物载体系统。以壳聚糖（CS）、长链聚乙烯醇（PVA-R）和带胆固醇基的聚丙烯酸（PAA）为包被剂，制备了二棕榈酰磷脂酰胆碱（DPPC）和磷酸二鲸蜡酯（DCP）（DPPC：DCP = 8：2）的多层脂质体。通过使用库尔特计数器的颗粒计数法在体外测量所得聚合物包覆的脂质体对大鼠肠的粘附性。将壳聚糖包覆的胰岛素脂质体给药于正常大鼠，监测血糖水平。通过测定脂质体的zeta电位证实了脂质体表面聚合物层的存在。CS包被脂质体显示出最高的粘膜粘附性，并且粘附程度取决于脂质体表面上CS的量。发现给药含有胰岛素的CS包覆脂质体后，大鼠的血糖水平显著降低。胰岛素脂质体给药后血糖水平持续降低超过12 h，表明CS包被脂质体在大鼠肠道中具有粘膜粘附作用。
Purpose. The mucoadhesiveness of polymer-coated liposomes was evaluated to develop a novel drug carrier system for oral administration of poorly absorbed drugs such as peptide drugs.Methods. Multilamellar liposomes consisting of dipalmitoylphosphatidylcholine (DPPC) and dicetyl phosphate (DCP) (DPPC:DCP = 8:2 in molar ratio) were coated with chitosan (CS), polyvinyl alcohol having a long alkyl chain (PVA-R) and poly (acrylic acid) bearing a cholesteryl group. The adhesiveness of the resultant polymer-coated liposomes to the rat intestine was measured in vitro by a particle counting method with a Coulter counter. The CS-coated liposomes containing insulin were administered to normal rats and the blood glucose level was monitored.Results. The existence of polymer layers on the surface of liposomes was confirmed by measuring the zeta potential of liposomes. The CS-coated liposomes showed the highest muco-adhesiveness and the degree of adhesion was dependent on the amount of CS on the surface of the liposomes. The blood glucose level of rats was found to be significantly decreased after administration of the CS-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 CS-coated liposomes in the intestinal tract of the rats.