Angelo Robert, Rousseau Kathleen, Grant Marshall, Leone-Bay Andrea, Richardson Peter
MannKind Corporation, Danbury, CT 06810, USA.
J Diabetes Sci Technol. 2009 May 1;3(3):545-54. doi: 10.1177/193229680900300320.
Technosphere Insulin (TI) is a novel inhalation powder for the treatment of diabetes mellitus. Technosphere Insulin delivers insulin with an ultra rapid pharmacokinetic profile that is distinctly different from all other insulin products but similar to natural insulin release. Such rapid absorption is often associated with penetration enhancers that disrupt cellular integrity.
Technosphere Insulin was compared to a panel of known penetration enhancers in vitro using the Calu-3 lung cell line to investigate the effects of TI on insulin transport.
Measures of tight junction integrity such as transepithelial electrical resistance, Lucifer yellow permeability, and F-actin staining patterns were all unaffected by TI. Cell viability and plasma membrane integrity were also not affected by TI. In contrast, cells treated with comparable (or lower) concentrations of penetration enhancers showed elevated Lucifer yellow permeability, disruption of the F-actin network, reduced cell viability, and compromised plasma membranes.
These results demonstrate that TI is not cytotoxic in an in vitro human lung cell model and does not function as a penetration enhancer. Furthermore, TI does not appear to affect the transport of insulin across cellular barriers.
技术球胰岛素（TI）是一种用于治疗糖尿病的新型吸入粉剂。技术球胰岛素能以超快速的药代动力学特征递送胰岛素，这与所有其他胰岛素产品明显不同，但类似于天然胰岛素释放。这种快速吸收通常与破坏细胞完整性的渗透促进剂有关。
在体外使用Calu-3肺细胞系将技术球胰岛素与一组已知的渗透促进剂进行比较，以研究TI对胰岛素转运的影响。
紧密连接完整性的指标，如跨上皮电阻、荧光素黄通透性和F-肌动蛋白染色模式均不受TI影响。细胞活力和质膜完整性也不受TI影响。相比之下，用相当（或更低）浓度的渗透促进剂处理的细胞显示荧光素黄通透性升高、F-肌动蛋白网络破坏、细胞活力降低和质膜受损。
这些结果表明，TI在体外人肺细胞模型中无细胞毒性，且不作为渗透促进剂起作用。此外，TI似乎不影响胰岛素跨细胞屏障的转运。
