pH-sensitive microparticles formed by combination of a synthetic copolymer and sodium alginate in presence of calcium chloride were prepared in mild conditions for specific water-soluble drug delivery. The copolymers of acryloxyethyl-trimethylammonium chloride and N-vinyl-2-pyrrolidone were synthesized by radical polymerization in aqueous solution at 60 degrees C using sodium persulfate as initiator. Fourier transform infrared spectroscopic characterization confirmed the structure of the copolymers and their compositions were determined by potentiometric method. Scanning Electron Microscopy study revealed that microparticles have a rough morphology with size ranging from 450 to 800 mu m as measured by optical microcopy. Cefotaxime as a model drug was encapsulated in the microparticles to evaluate the in vitro release behavior under different pH conditions. At physiological temperature, the amount of drug released increased with increasing pH. The amount of drug release from microparticles after 24 h (84%) was more extensive in simulated intestinal fluid when compared with acidic pH environment (20%). These preliminary results suggest that the new microparticles can be used as good candidate for oral drug controlled release in the treatment to colon diseases. POLYM. ENG. SCI., 55:981-987, 2015. (c) 2014 Society of Plastics Engineers