Specific permeability modulation of intestinal paracellular pathway by chitosan-poly(isobutylcyanoacrylate) core-shell nanoparticles

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Abstract

This work is focused on the evaluation of the in vitro permeation modulation of chitosan and thiolated chitosan (chitosan-TBA) coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles as drug carriers for mucosal administration. Core-corona nanoparticles were obtained by radical emulsion polymerisation of isobutylcyanoacrylate (IBCA) with chitosan of different molecular weights and different proportions of chitosan/chitosan-TBA. In this work, the effect of these nanoparticles on the paracellular permeability of intestinal epithelium was investigated using the Ussing chamber technique, by adding nanoparticle suspensions in the mucosal side of rat intestinal mucosa. Results showed that permeation of the tracer [14C]mannitol and the reduction of transepithelial electrical resistance (TEER) in presence of nanoparticles were more pronounced in those formulations prepared with intermediate amounts of thiolated polymer. This effect was explained thanks to the high diffusion capacity of those nanoparticles through the mucus layer that allowed them to reach the tight junctions in higher extent.

It was concluded that, although a first contact between nanoparticles and mucus was a mandatory condition for the development of a permeation enhancement effect, the optimal effect depended on the chitosan/chitosan-TBA balance and the conformational structure of the particles shell.

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