Behavior of mucoadhesive nanoparticles having hydrophilic polymeric chains in the intestine.

The behavior of nanoparticles having surface hydrophilic poly(N-isopropylacrylamide), poly(N-vinylacetamide), poly(vinylamine) or poly(methacrylic acid) chains in the intestine was examined. The permeability of salmon calcitonin (sCT) from the mucosal to serosal side of the everted jejunum was enhanced in the presence of nanoparticles. This enhancement, which correlated with the amount of sCT incorporated in nanoparticles, disappeared completely after removal of the mucous layer. When fluorescein isothiocyanate-dextran (FD-4) was used instead of sCT, its permeability through the everted jejunum with and without mucous layer was not enhanced by any nanoparticles, because FD-4 was not incorporated in nanoparticles at all. These findings indicated that the accumulation of nanoparticles incorporating sCT in the mucous layer resulted in the enhancement of sCT permeability. Nanoparticles with poly(N-isopropylacrylamide) or poly(vinylamine) on their surfaces did not cause any damage to the intestinal mucosa. Also, none of the nanoparticles opened the tight junction of the intestinal membrane. It was concluded that mucoadhesion of nanoparticles incorporating sCT to the gastrointestinal mucosa contributed to the absorption enhancement of sCT.