Cellular evaluation of insulin transmucosal delivery

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摘要：

P(MAA-g-EG) microparticles have been extensively investigated as carriers for oral delivery of proteins such as insulin. In this study, we investigated the effect of the molecular weight of the PEG tethered chains in the copolymer network and of the microparticle size on the transepithelial electrical resistance (TEER) and insulin epithelial permeability, using monolayers of human intestinal epithelial Caco-2 cells. Two molecular weights of the PEG chains, 400 and 1000, were investigated, as well as three different dry microparticle sizes: 25-90, 90-150 and 150-212 m. Their effect on the cell monolayer integrity was studied by monitoring TEER as a fraction of time and determining insulin permeability. The presence of insulin-loaded P(MAA-g-EG) microparticles decreases the TEERs value by 50% with respect to the control. This disruption of the cell monolayer was recovered in 3 h after the removal of the polymer microparticles. Within the range of PEG molecular weights studied, there was no significant change of the TEER values. However, decreased microparticle sizes and short PEG chains systems led to higher permeability values. Insulin-loaded P(MAA-g-EG) microparticles enhanced the transport of insulin through the Caco-2 cell monolayers.

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关键词：

Experimental/ biochemistry biodiffusion biomedical materials biomembrane transport drug delivery systems molecular biophysics molecular weight monolayers permeability polymer blends polymer gels proteins/ insulin transmucosal delivery oral delivery P(MAA-g-EG) microparticle protein molecular weight effect polyethyleneglycol tethered chain copolymer network transepithelial electrical resistance insulin epithelial permeability human intestinal epithelial Caco-2 cell cell monolayer integrity transmucosal permiability insulin transport 25 to 90 micron 90 to 150 micron 150 to 212 micron 3 h/ A8770J Prosthetics and other practical applications A8725D Biological transport cellular and subcellular transmembrane physics A3620F Molecular weights of macromolecules A8720E Natural and artificial biomembranes A8715D Physical chemistry of biomolecular solutions condensed states/ size 2.5E-05 to 9.0E-05 m size 9.0E-05 to 1.5E-04 m size 1.5E-04 to 2.12E-04 m time 1.1E+04 s