A convenient approach has been developed for the preparation of microsize hydrogels composed of crosslinked poly(acrylic acid) (PAA) and poly(N-isopropylacrylamide) (PNIPAm). First, semi-interpenetration polymer networks of hydropropylcellulose (HPC) and PNIPAm-co-PAA copolymer are formed through the copolymerization and crosslinking of monomer acrylic acid and N-isopropylacrylamide in HPC aqueous solution. After the selective removal of HPC from networks due to ionization of PAA units and disruption of hydrogen bonding with increasing pH, PNIPAm-co-PAA microgels are obtained, whose volume is confirmed to be responsive to both temperature and pH. Doxorubicin hydrochloride (Dox) can be encapsulated in PNIPAm-co-PAA microgels with high drug loading driven by the electrostatic interaction, and a sustained-release characteristic of Dox from the microgels is observed under physiological pH value and temperature. In vitro cell experiments, the drug-loaded microgels can be taken up by LoVo cells and release their payload in cell cytoplasm without loss of drug efficacy. This indicates that PNIPAm-co-PAA microgels might be a potential drug delivery carriers especially for water-soluble or polypeptide drugs. (c) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011