Mucoadhesion of polystyrene nanoparticles having surface hydrophilic polymeric chains in the gastrointestinal tract

The mucoadhesion of polystyrene nanoparticles having surface hydrophilic po lymeric chains in the gastrointestinal (GT) tract was investigated in rats. Radiolabeled nanoparticles were synthesized by adding hydrophobic 3-(trifl uoromethyl)-3-(m -[I-125]iodophenyl)diazirine in the final process of nanop article preparation. The radioiodonated diazirine seemed to be incorporated in the hydrophobic polystyrene core of nanoparticles. The incorporation ra te was less than 10%, irrespective of nanoparticle type. The diazirine inco rporated in nanoparticles exhibited little leakage from them even though th ey were mixed with a solution corresponding to GI juice. The change in bloo d ionized calcium concentration after oral administration of salmon calcito nin (sCT) with nanoparticles showed that the in vivo enhancement of sCT abs orption by radiolabeled nanoparticles was the same as that by non-labeled n anoparticles. The GI transit rates of nanoparticles having surface poly(N-i sopropylacrylamide), poly(vinylamine) and poly(methacrylic acid) chains, wh ich can improve sCT absorption, were slower than that of nanoparticles cove red by poly(N-vinylacetamide), which does not enhance sCT absorption at all . These dow transit rates were probably the result of mucoadhesion of nanop articles. The strength of mucoadhesion depended on the structure of the hyd rophilic polymeric chains on the nanoparticle surface. The mucoadhesion of poly(N-isopropylacrylamide) nanoparticles, which most strongly enhanced sCT absorption, was stronger than that of ionic nanoparticles, and poly(N-viny lacetamide) nanoparticles probably did not adhere to the GI mucosa. These f indings demonstrated that there is a good correlation between mucoadhesion and enhancement of sCT absorption. (C) 1999 Elsevier Science B.V. All right s reserved.