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        Transportation efficiency of insulin loaded in agarose-grafting-hyaluronan microparticle crossing Coca-2 cell monolayer

        JianYan Huang,Lingmin Zhang,Peng Chen,Shitao Chen,Yueheng Wu,ShunQing Tang 한국물리학회 2011 Current Applied Physics Vol.11 No.3

        Agarose-grafting-hyaluronan (Ag-g-HA) has been proved to be a potential carrier for oral insulin, but it needs to clarify that insulin loaded in Ag-g-HA microparticle is effectively transported across epithelial layer. In this paper, Caco-2 cell monolayer was used for imitation of epithelial layer in small intestine to evaluate Ag-g-HA copolymer enhanced insulin transportation crossing epithelial layer. Ag-g-HA/insulin polyelectrolyte complexes were formed via electrostatic interaction at pH 3e5.4 and could spontaneously form microparticles with average diameter of 2 μm. Caco-2 cells in transwell dish were attached in tight monolayer after 21 d proliferation, and some features of Caco-2 cell monolayer, such as trans-epithelial electrical resistance (TEER) value being over 400 Ω/cm^2, alkaline phosphatase (ALP) activity being 0.7184 ± 0.095, and apparent permeability coefficient value (Papp) of propranonol being 1 × 10^-6 cm/s,were similar to those of epithelial layer in small intestine. These results revealed that Caco-2 cellmonolayer was suitable to be a model of small intestine epithelium layer for imitation of insulin crossing small intestine. P_app of insulin crossing Caco-2 monolayer reached 0.592 ± 0.067 × 10^-6 cm/s, which was significantly greater than the control groups. This meant Ag-g-HA as insulin carrier significantly promoted insulin crossing Caco-2 cell monolayer. These findings demonstrate that Caco-2 cell monolayer is a suitable model for drug transportation crossing epithelial layer, and Ag-g-HA has a promise as oral insulin carrier.

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