Seki Toshinobu, Fukushi Nanako, Maru Hiroto, Kimura Soichiro, Chono Sumio, Egawa Yuya, Morimoto Kazuhiro, Ueda Hideo, Morimoto Yasunori
Faculty of Pharmaceutical Sciences, Josai University.
Yakugaku Zasshi. 2011 Feb;131(2):307-14. doi: 10.1248/yakushi.131.307.
Sperminated pullulans (SP) having different molecular weights (MWs) were prepared, and the enhancing effect on the pulmonary absorption of insulin in rats was examined. SP acted as enhancers of insulin absorption when a 0.1% solution was applied with insulin simultaneously and their enhancing effects depended on the MW of the SP; the same solutions exhibited low toxicity in the in vivo LDH leaching test. In the in vitro experiments using Calu-3 cells, tight junction-opening effects and a toxic effect of SP in the MTT assay were observed at lower concentrations compared with the in vivo experiments. A mucus layer might interfere with the interaction between SP and the cell surface and might suppress both these effects and toxicity. SP having a high MW will be useful for preparing safe and efficient formulations of peptide and protein drugs. The change in the localization of the tight junction proteins may be related to the permeation-enhancing mechanism of SP.
制备了具有不同分子量（MW）的发芽普鲁兰多糖（SP），并研究了其对大鼠肺部胰岛素吸收的增强作用。当同时应用0.1%的溶液与胰岛素时，SP可作为胰岛素吸收的增强剂，其增强作用取决于SP的分子量；相同溶液在体内乳酸脱氢酶释放试验中表现出低毒性。在使用Calu-3细胞的体外实验中，与体内实验相比，在较低浓度下观察到SP在MTT试验中的紧密连接开放效应和毒性作用。黏液层可能会干扰SP与细胞表面之间的相互作用，并可能抑制这两种效应和毒性。具有高分子量的SP将有助于制备安全有效的肽和蛋白质药物制剂。紧密连接蛋白定位的变化可能与SP的渗透增强机制有关。
