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J Drug Deliv Sci Technol. 2008 Jan;18(1):47-50.

Quantifying Tight Junction Disruption Caused by Biomimetic pH-Sensitive Hydrogel Drug Carriers.

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Biomaterials, Drug Delivery, Bionanotechnology and Molecular Recognition Laboratories, The University of Texas at Austin, Austin, TX, 78712, U.S.A.


Facilitation of protein transport across biomimetic polymers and carriers used in drug delivery is a subject of major importance in the field of oral delivery. Quantitative immunofluorescence of epithelial tight junctions can be a valuable tool in the evaluation of paracellular permeation enhancement and macromolecular drug absorption. The tight junctional space is composed of transmembrane protein networks that provide both mechanical support and a transport barrier. Both of these may be affected by drug delivery agents that enhance paracytosis. Imaging is the only tool that can tease apart these processes. A confocal microscopy imaging method was developed to determine the effect of microparticulate poly(methacrylic acid) grafted poly(ethylene glycol) (P(MAA-g-EG)) hydrogel drug carriers on the integrity of claudin-1 and E-cadherin networks in Caco-2 monolayers. Z-stack projection images showed the lateral disruption of tight junctions in the presence of drug carriers. Tight junction image fraction measurements showed more significant differences between membranes exposed to microparticles and a control group. Mechanical disruption was much more pronounced in the presence of P(MAA-g-EG) microparticles as compared to the effect of EDTA.

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