Zheng Jianheng, Zheng Yi, Chen Jiayin, Fang Fang, He Jiake, Li Ning, Tang Yue, Zhu Jiabi, Chen Xijing
Key Laboratory of General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai, China.
Pharmazie. 2012 May;67(5):448-51.
Natural pulmonary surfactant (PS) and its artificial substitute phospholipid hexadecanol tyloxapol (PHT) are effective absorption enhancers on promoting recombinant human insulin (Rh-ins) absorption in vivo, but the in vitro efficacy and underlying mechanism remains unclear. In the current study, the permeation promoting effects of PS and PHT of insulin through Calu-3 monolayers in Transwell were evaluated. The viability of Calu-3 cells on conducting the permeation study was confirmed by TER and Electron Microscopy. Both PS and PHT significantly enhanced the permeation of Rh-ins and FD4 through calu-3 cells, with PS having a greater absorption enhancing effect than that of PHT. PS and PHT may interact directly with the tight junctions between cells and then result in intercellular permeation of peptide drugs. LDH release assay showed no significant acute toxicity of PS and PHT. The results indicated that these absorption enhancing agents may be useful as an absorption enhancer for pulmonary delivery of peptide and protein drugs.
天然肺表面活性剂（PS）及其人工替代品磷脂十六醇泰洛沙泊（PHT）是促进重组人胰岛素（Rh-ins）体内吸收的有效吸收促进剂，但体外疗效及潜在机制尚不清楚。在本研究中，评估了PS和PHT对胰岛素透过Transwell中Calu-3单层细胞的渗透促进作用。通过跨上皮电阻（TER）和电子显微镜确认了进行渗透研究时Calu-3细胞的活力。PS和PHT均显著增强了Rh-ins和FD4透过Calu-3细胞的渗透，PS的吸收增强作用比PHT更大。PS和PHT可能直接与细胞间紧密连接相互作用，进而导致肽类药物的细胞间渗透。乳酸脱氢酶（LDH）释放试验表明PS和PHT无明显急性毒性。结果表明，这些吸收促进剂可能作为肽和蛋白质药物肺部给药的吸收促进剂。
