In this article, novel smart hydrogels based on biodegradable pH sensitive poly(L-glutamic acid-g-2-hydroxylethyl methacrylate) (PGH) chains and temperature-sensitive hydroxypropylcellulose-g-acrylic acid (HPC-g-AA) segments were designed and synthesized. The influence of pH and temperature on the equilibrium swelling ratios of the hydrogels was discussed. The optical transmittance of the hydrogels was also changed as a function of temperature, which reflecting that the HPC-g-AA part of the hydrogels became hydrophobic at the temperature above the lower critical solution temperature (LCST). At the same time, the LCST of the hydrogels had a visible pH-dependent behavior. Scanning electron microscopic analysis revealed the morphology of the hydrogels before and after enzymatic degradation. The biodegradation rate of the hydrogels was directly related to the PGH content and the pH value. The in vitro release of bovine serum albumin from the hydrogels were investigated. The release profiles indicated that both the HPC-g-AA and PGH contents played important roles in the drug release behaviors. These results show that the smart hydrogels seem to be of great promise in pH-temperature oral drug delivery systems. (C) 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 49: 2941-2951, 2011