The purpose of this study was to produce pH-sensitive domain in the dense poly(ethylene-co-vinyl-alcohol) (EVAL) membrane for colonic delivery of anti-cancer drug 5-fluorouracil (5-FU) by blending with a small amount of poly(acrylic acid) (PAA). The Fourier transform infrared (FTIR) spectroscopy analysis shows that PAA and EVAL were not very compatible in the PAA/EVAL blended membrane, whereas the intensity of self-association of both polymers was higher than that of inter-association between PAA and EVAL. It was proposed that PAA molecules would aggregate to act as the access for the transport of 5-FU through the blended membranes. The aggregated PAA gel phases were beyond the observable sensitivity of the scanning electron microscopy (SEM) and were low permeable for 5-FU at low pH, but significantly improved the permeability of 5-FU by the increase of pH of the medium, which agreed with the application of colon-specific drug delivery. When the membrane preparation temperature was changed from 60 to 45 degrees C, PAA domain contained in the blended membrane did not affect the permeation rate of 5-FU at different pH. This is because the membrane prepared at 45 degrees C was not so dense as that prepared at 60 degrees C. Therefore, the pH-sensitive characteristic of PAA domains would be applicable only to the membrane with a dense structure. Finally, it was demonstrated that 5-FU separated by the blended membranes still exhibited cytotoxicitiy toward Caco-2 cells at pH 7.4. Thus, the PAA/EVAL blended membrane is a potential material for the specific delivery of 5-FU to the colon for local treatment of colorectal cancer in the future clinical application. (c) 2005 Elsevier B.V. All rights reserved.