The aim of this work is to explore a microcapsule formulation applicable for a peroral colon-specific delivery of water-soluble macromolecules such as peptide drugs, based on our previous delayed-release formulations using self-made colloidal terpolymers of ethyl acrylate, methyl methacrylate and 2-hydroxyethyl methacrylate (poly(EA/MMA/HEMA)). Peptides are thermally unstable and less permeable through a polymeric membrane in general. Thus, the present work was intended to establish the acrylic terpolymers having the following characteristics: an excellent film-formability even at a low process-temperature of 40 degreesC to preserve the stability of heat-sensitive drugs and a desired permeability allowing a delayed-release profile of macromolecular drugs. Using various types of poly(EA/MMA/HEMA) synthesized with different monomer molar ratios, microencapsulation of the particles consisting of a lactose core and a surface-layer of water-soluble fluorescence-labeled dextran (FITC-Dex, Mw 9500), a model of macromolecular solute, was carried out by the Wurster process. The release profiles of FITC-Dex were highly dependent on the terpolymer compositions. The increased EA content made the poly(EA/MMA/HEMA) films flexible and less permeable, leading to significant decrease in release rate of FITC-Dex. Contrary, it was found that the increase in HEMA content enhanced the FITC-Dex release due to the enhanced hydration of the films, as expected from its higher hydrophilicity than the other monomers. Among a series of poly(EA/MMA/HEMA) prepared here, the poly(EA/MMA/HEMA) with the molar ratio of 95:85:40 exhibited a good film-formability in the post-thermal curing process at 40 degreesC. The established coating films allowed delayed-release of the microencapsulated FITC-Dex; the profile was characterized by a lag time and subsequent rapid release. This delayed-release was probably due to time-dependent change of the semi-permeable nature of the hydrated coating films as a consequence of anomalous film-deformation arising from the osmotic pressure inside the microcapsules. Moreover, the release profiles of FITC-Dex were found to be pH-independent. Based on our findings, the use of poly(EA/MMA/HEMA) with molar ratio of 95:85:40 could be proposed as a feasible way to prepare a delayed-release microcapsule containing water-soluble macromolecules by the Wurster coating process, toward the future application to colon-specific delivery of peptide drugs. (C) 2004 Elsevier B.V. All rights reserved.