Enhanced pulmonary absorption of recombinant human insulin by pulmonary surfactant and phospholipid hexadecanol tyloxapol through Calu-3 monolayers.

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.