Seki Toshinobu, Kanbayashi Hiroshi, Chono Sumio, Tabata Yasuhiko, Morimoto Kazuhiro
Hokkaido Pharmaceutical University School of Pharmacy, 7-1 Katsuraoka-cho, Otaru, Hokkaido 047-0264, Japan.
Int J Pharm. 2007 Jun 29;338(1-2):213-8. doi: 10.1016/j.ijpharm.2007.02.004. Epub 2007 Feb 9.
The effects of a sperminated gelatin (SG), which was prepared as a candidate absorption enhancer by the addition of spermine to gelatin, on the nasal absorption of insulin, were examined in rats. The AUC of immuno-reactive insulin levels in the plasma after nasal administration of insulin were increased 5.3-fold by addition of 0.2% SG, and the plasma glucose levels fell in a manner dependent on the insulin levels. In Calu-3 cell monolayer permeation experiments, SG showed significant enhancing effects on 5(6)-carboxyfluorescein (CF), FITC-dextran (MW 4400, FD4) and insulin. Evaluation of the tight junctions in the Calu-3 cell monolayers based on the Renkin molecular sieving function suggests that the pore occupancy/length ratio of the permeation pathways for water-soluble molecules in the tight junctions increases, while the equivalent cylindrical pore radius is not changed by SG treatment. SG may transform the true tight junctions, which act as a barrier for water-soluble molecules, into pathways for CF and FD4 to increase their number. SG is a good candidate for a safe absorption enhancer to produce a slight modification of the permeability of the paracellular pathway of mucosal membranes, while retaining the sieving property of the epithelial membranes.
通过向明胶中添加精胺制备的精胺化明胶（SG）作为一种候选吸收增强剂，对大鼠胰岛素鼻腔吸收的影响进行了研究。鼻腔给予胰岛素后，血浆中免疫反应性胰岛素水平的AUC在添加0.2% SG时增加了5.3倍，并且血浆葡萄糖水平以依赖于胰岛素水平的方式下降。在Calu-3细胞单层渗透实验中，SG对5(6)-羧基荧光素（CF）、异硫氰酸荧光素标记的葡聚糖（分子量4400，FD4）和胰岛素显示出显著的增强作用。基于Renkin分子筛分功能对Calu-3细胞单层紧密连接进行评估表明，紧密连接中水溶性分子渗透途径的孔隙占有率/长度比增加，而等效圆柱孔半径在SG处理后未发生变化。SG可能将作为水溶性分子屏障的真正紧密连接转变为CF和FD4的渗透途径，从而增加其数量。SG是一种安全的吸收增强剂的良好候选物，它能对粘膜细胞膜旁细胞途径的通透性进行轻微改变，同时保留上皮细胞膜的筛分特性。
