Coughlan D C, Corrigan O I
School of Pharmacy and Pharmaceutical Sciences, University of Dublin, Trinity College Dublin, Dublin 2, Ireland.
J Pharm Sci. 2008 Jan;97(1):318-30. doi: 10.1002/jps.21095.
Swelling and concomitant drug-release kinetics from a series of poly(N-isopropylacrylamide) (PNIPA) matrices were examined. Scanning electron microscopy indicated a decrease in polymer pore/mesh size above the lower critical solution temperature (LCST) with increasing percentage crosslinker. The release of sodium benzoate (NaB) or benzoic acid (BA) were investigated above and below the LCST of the gels and compared to the drug-loaded gel-swelling rates. The release rate of NaB increased with increasing percentage crosslinker above the LCST in contrast to a decrease in release rate with increasing crosslinker seen previously with non-thermoresponsive hydrogel systems. As the percentage crosslinker increased, there was therefore a decrease in the ability to thermally control the release of this small model drug. In contrast to the crosslinker-dependent pattern apparent with NaB, drug-PNIPA hydrophobic binding controlled the swelling rate of BA-loaded hydrogels. As a result, all the BA-loaded systems showed similar diffusion controlled swelling and release patterns, effectively independent of the inherent-swelling rates of the hydrogels. The crosslinking content of the hydrogel and the physicochemical nature of the loaded drug were therefore shown to be important in thermal control of drug release from PNIPA hydrogels.
研究了一系列聚（N-异丙基丙烯酰胺）（PNIPA）基质的溶胀和伴随的药物释放动力学。扫描电子显微镜表明，在较低临界溶液温度（LCST）以上，随着交联剂百分比的增加，聚合物孔/网尺寸减小。在凝胶的LCST上下研究了苯甲酸钠（NaB）或苯甲酸（BA）的释放，并与载药凝胶的溶胀速率进行了比较。与之前在非热响应水凝胶系统中观察到的随着交联剂增加释放速率降低相反，在LCST以上，NaB的释放速率随着交联剂百分比的增加而增加。因此，随着交联剂百分比的增加，热控释这种小模型药物的能力下降。与NaB明显的交联剂依赖性模式不同，药物-PNIPA疏水结合控制了载BA水凝胶的溶胀速率。结果，所有载BA系统均显示出相似的扩散控制溶胀和释放模式，有效地独立于水凝胶的固有溶胀速率。因此，水凝胶的交联含量和所载药物的物理化学性质在热控PNIPA水凝胶药物释放中很重要。
