Abstract:
Aim: Amide-linked amylose-based prodrugs were developed for colon-targeted release of mefenamic acid. Materials & methods: Activation of prodrug was studied spectrophotometrically, enzyme-linked immunosorbent assay appraised cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition at different concentrations of the prodrug, the behavior of prodrug under physiological conditions was monitored by scanning electron microscopy. Results: Prodrug was poorly activated in the enzyme-free simulated gastric media and simulated intestinal media (SIM) but preincubation in pancreatin followed by treatment in aminopeptidase containing SIM led to a significant activation of prodrug. Conclusion: Amide-linked amylose-mefenamic acid conjugates showed a slow release in simulated gastric media and a controlled release in SIM with pancreatin playing an important role in drug release.
摘要:
目的:开发了基于酰胺连接的直链淀粉的前药,用于甲芬那酸的结肠靶向释放。材料与方法:用分光光度法研究了前药的活化,酶联免疫吸附试验评价了不同浓度的前药对环氧合酶-1(COX-1)和环氧合酶-2(COX-2)的抑制作用,通过扫描电子显微镜监测前药在生理条件下的行为。结果:前药在无酶的模拟胃介质和模拟肠介质(SIM)中的活化能力较差,但在胰酶中预孵育,然后在含氨肽酶的SIM中处理导致前药的显着活化。结论:酰胺连接的直链淀粉-甲芬那酸缀合物在模拟胃介质中显示出缓慢释放,在SIM中显示出受控释放,而胰酶在药物释放中起重要作用。