Phthalyl chitosan (PC) was synthesized and phthalyl chitosan-poly(ethylene oxide) (PCP) semi-interpenetrating network microparticles were developed by ionic crosslinking with sodium tripolyphosphate. The characterization of PCP particles was done, and these particles were compared with PC and native chitosan (NC) microparticles. The PCP particle size was around 1.3 mu m with a potential of about -28.6 +/- 12.6 mV and an insulin loading efficiency of 89.6%. The release studies were done at pH 1.2 and 7.4, which indicated a minimal release at pH 1.2 compared to that at pH 7.4. The degree of swelling was observed to be higher in PCP than in PC or NC particles. The in vitro mucin-binding capacity and the intestinal mucoadhesiveness of the particles were evaluated. The PCP particles were highly mucoadhesive, and correspondingly, the mucin-binding capacity was lower for these particles; this is necessary for any matrix to be a successful mucoadhesive. These results suggest the usefulness of these particles as a potential candidate for oral insulin-delivery systems. (C) 2008 Wiley Periodicals, Inc. J Appl Polym Sci 110: 2787-2795, 2008