Novel poly(N-isopropylacrylamide) (PNI-PAAm)/chitosan (CS) semi-interpenetrating polymer network hydrogel particles were prepared by inverse suspension polymerization. The prepared particles were sensitive to both temperature and pH, and they had good reversibility in solution at different temperatures and pH values. The swelling ratios of PNIPAAm/CS hydrogel particles decreased slightly with the addition of CS, which did not shift the lower critical solution temperature. The drug-release behavior of the particles was investigated using cyclic adenosine 3',5'-monophosphate (CAMP) as a model drug. The release of cAMP from the hydrogel particles was affected by temperature, pH, and the CS content in the particles. These results showed that semi-IPN hydrogen particles appeared to be of great promise in pH- and temperature-sensitive oral drug release. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 116: 1342-1347, 2010