Microcapsules prepared from blends of poly(d,l-lactide-coglycolide) with a lactide:glycolide ratio of 75:25 (PLGA75:25) and poly-(d,l-lactide) (PLA5000) or poly(d,l-lactic acid-co-glycolic acid) (PLGA5000) were dispersed in phosphate-buffered saline, and their hydrolytic rates were investigated. Using the Henderson-Hasselbalch equation and an L-lactic acid experiment, the concentration of hydrogen ions released into the bulk medium was calculated from the change in buffer pH. The rate of H+ formation was found to be dependent upon the polymer composition of the microcapsules. The incorporation of PLGA5000 or PLA5000 into PLGA75:25 microcapsules drastically enhanced hydrolytic rates of microcapsules and resulted in controlled release of hydrogen ions generated from carboxyl end groups of both intact and degrading polymers. In contrast to microcapsules prepared with PLGA75:25 only, which liberated a negligible amount of H+ ions after a 21-day incubation, the microcapsules prepared from polymer blends released approximately (19.2-42.0) (x10(-3)) mmol of H+ ions. It has been found that the amount of hydrogen ions liberated into the bulk can be used as a qualitative indicator to monitor the change in microcapsule permeability to protein as well as polymer degradation.
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