ABSTRACT:In the present study, microparticles composed of polymethacrylic acid-chitosan (PMAA-CS) were prepared by a novel interionic gelation method. Free-radical polymerization of methacrylic acid was carried out in the presence of CS, using a water-soluble initiator, and application of these microparticles toward oral insulin delivery was evaluated. Microparticles obtained were characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) studies. From SEM studies, it was observed that microparticles had an aggregated morphology with size ϳ20 m, while FTIR confirmed the presence of ionic interaction between PMAA and CS chains. Protein loading was done by diffusion filling method, and from in vitro release study, it was observed that insulin-loaded microparticles displayed a pH depended release profile at alkaline/acidic pH. Microparticles exhibited sustained release of insulin for 3-4 h at neutral pH, and enzyme linked immunosorbent assay (ELISA) proved that encapsulated protein maintained 100% biological activity at neutral pH. Preliminary study suggests that these microparticles can serve as good candidate for oral protein delivery.