Uptake and transport of poly( N-vinylpyrrolidone-co-maleic acid) by the adult rat small intestine cultured in vitro: Effect of chemical structure

Abstract

To study the structure-activity relationships of polymer uptake and transfer across the gastrointestinal mucosa, poly( N-vinylpyrrolidone-co-maleic acid) (NVP MA) polymers of standardised molecular mass (20000 Da) were synthesised to contain side-chains of different charge or hydrophobicity. All polymers additionally contained tyrosinamide residues to permit radioiodination. Using an improved everted gut sac prepared from adult rat small intestine, the tissue accumulation and serosal transport of the polymers was measured in vitro over a 2 h incubation period. All polymers were captured by the tissue linearly with time (endocytic indices between 1.6 and 16 μl/mg protein per h), and then transferred slowly to the serosal fluid (endocytic indices between 0.18 and 2 μl/mg protein per h). The neutral NVP MA polymer showed the lowest rate of tissue association, but this was increased 5-fold by the presence of either negatively or positively charged groups. The maximum rate of transport across the mucosa was seen for the most negatively charged polymer derivative, this being equivalent to approx. 26% its rate of tissue accumulation. Increasing hydrophobicity of the polymer derivatives had a more pronounced effect on the rate of tissue capture, increasing it by up to 10-fold for the most hydrophobic derivative. However, in this case, the serosal transfer was only 10–15% the rate of tissue uptake. The data presented indicate that NVP MA polymers can be tailor-made for use in oral delivery systems. Substituent groups can be incorporated to promote tissue uptake or translocation across the gastrointestinal mucosa, or a combination of the two.