Sah H, Chien Y W
Controlled Drug-Delivery Research Center, Rutgers State University of New Jersey, Piscataway 08854, USA.
J Pharm Sci. 1995 Nov;84(11):1353-9. doi: 10.1002/jps.2600841117.
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.
由丙交酯与乙交酯比例为75:25的聚（d，l-丙交酯-乙交酯共聚物）（PLGA75:25）与聚（d，l-丙交酯）（PLA5000）或聚（d，l-乳酸-乙醇酸共聚物）（PLGA5000）的共混物制备的微胶囊分散于磷酸盐缓冲盐水中，并对其水解速率进行了研究。利用亨德森-哈塞尔巴尔赫方程和L-乳酸实验，根据缓冲液pH值的变化计算释放到本体介质中的氢离子浓度。发现H⁺形成速率取决于微胶囊的聚合物组成。将PLGA5000或PLA5000掺入PLGA75:25微胶囊中可显著提高微胶囊的水解速率，并导致完整聚合物和降解聚合物的羧基端基产生的氢离子可控释放。与仅用PLGA75:25制备的微胶囊不同，后者在孵育21天后释放的H⁺离子量可忽略不计，而由聚合物共混物制备的微胶囊释放了约（19.2 - 42.0）×10⁻³ mmol的H⁺离子。已发现释放到本体中的氢离子量可作为定性指标，用于监测微胶囊对蛋白质的渗透性变化以及聚合物降解情况。
