Abstract
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. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
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