Blend microspheres of poly(3-hydroxybutyrate) (PHB) and cellulose acetate phthalate (CAP) have been prepared in compositions of 2:1, 1:1, and 1:3 (w/w) by the solvent evaporation technique. These pH-sensitive polymers were utilized to investigate the colon delivery of 5-fluorouracil (5-FU), an anticancer drug. The surface morphology of the microspheres was studied by scanning electron microscopy (SEM), which confirmed their spherical nature with sizes ranging from 29 to 67 mu m, as well as pore structures before and after the dissolution experiments. Fourier transform infrared (FTIR) spectroscopy was used to confirm the polymer blend compatibility and to confirm the absence of drug-polymer interactions. Differential scanning calorimetry (DSC) was employed to study the crystalline nature and molecular-level dispersion of 5-FU in the matrixes after encapsulation. In vitro release experiments were performed at 37 degrees C in simulated buffer medium of the stomach (pH 1.2) for 2 h, followed by simulated intestinal medium (pH 7.4). It was found that the release of 5-FU from blend microspheres followed pH-dependent release as compared to that of plain PHB microspheres. From the in vitro release studies, it was found that blend microspheres are more efficient at delivering 5-FU to the colon than plain PHB microspheres. Furthermore, release data were fitted to empirical equations to understand the nature of the drug release profiles.