To develop a novel pH-sensitive PEGylated carrier for protein-based anticancer agents, we modified bovine serum albumin (BSA) with poly(ethylene glycol) citrate ester (PEG-CA) through amidation with its amino groups. Increasing the mixing ratio of albumin from 3 to 6 with respect to PEG-CA resulted in a 2-fold increase in the degree of albumin modification. Adriamycin (ADR)-loaded PEG-CA-BSA hydrogels and microparticles were prepared, and the cumulative amounts of ADR released from the PEG-CA-BSA hydrogels (phosphate-buffered saline, pH 7.4) showed that all the PEG-CA-BSA((x)) (x represents degree of substitution of PEG to amino group of albumin, i.e. 26%, 28%, 31% and 49%) hydrogels had lower ADR release rates with a slight initial burst release. During the first 24 h, the cumulative releases were 15.5% for PEG-CA-BSA((49)), 24% for PEG-CA-BSA((31)), 31% for PEG-CA-BSA((28)), and 38% for PEG-CA-BSA((26)). Afterward, all the release rates slowed, and they were almost in the following order: PEG-CA-BSA((26)) > PEG-CA-BSA((28)) > PEG-CA-BSA((31)) > PEG-CA-BSA((49)). The release rates of ADR from the microparticles were dependent on the amount of glutaraldehyde. According to our findings, a higher PEG-CA/BSA molar ratio led to a reduced cumulative amount of ADR released from the hydrogels, whereas higher release rates were observed for microparticles with a lower amount of BSA in the conjugates in a pH-dependent manner. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 2635-2643, 2011