基于直链淀粉的非甾体抗炎药芬那酸酯前药的合成与释放研究。
Synthesis and release studies on amylose-based ester prodrugs of fenamic acid NSAIDs.
机构信息
Department of Chemistry, University of Petroleum & Energy Studies, Dehradun, 248007, India.
Department of Chemistry, Uttaranchal University, Dehradun, 248007, India.
出版信息
Ther Deliv. 2024;15(10):769-779. doi: 10.1080/20415990.2024.2400041. Epub 2024 Sep 17.
To achieve colon-targeted release of mefenamic acid from its ester-linked amylose prodrugs. The prodrug was characterized by 1H NMR and IR spectroscopy. Drug activation and release profile was studied in enzyme enriched simulated physiological media via UV-vis spectroscopy and was validated with HPLC analysis. ELISA assay was employed for evaluating the % inhibition of COX-1 and COX-2 inhibition at different concentrations of the prodrug preincubated with ester and/ or amylose hydrolyzing enzymes. SEM studies further validated the performance of the prodrug under simulated physiological conditions. Pancreatin was essential for the prodrug activation in SIM to make the ester bonds in prodrug vulnerable to hydrolysis by esterase. This evidence was confirmed by drug release studies, HPLC analysis, ELISA assay and SEM investigation where the ester conjugated prodrug showed marked stability in physiological media only to get activated in the presence of amylose degrading enzyme. Ester linked amylose-mefenamic acid conjugate showed both enzyme responsive activation and release in SIM.
为了实现米非司酮从其酯键连接的淀粉酯前药中结肠靶向释放。通过 1H NMR 和 IR 光谱对前药进行了表征。通过紫外可见光谱法在富含酶的模拟生理介质中研究了药物的激活和释放特性，并通过 HPLC 分析进行了验证。采用 ELISA 测定法评价不同浓度的前药在与酯酶和/或淀粉水解酶预孵育时对 COX-1 和 COX-2 抑制的%抑制。SEM 研究进一步验证了在模拟生理条件下前药的性能。在 SIM 中，胰蛋白酶对于前药的激活是必不可少的，以使前药中的酯键易于被酯酶水解。这一证据通过药物释放研究、HPLC 分析、ELISA 测定和 SEM 研究得到了证实，其中在生理介质中，酯结合的前药仅在存在淀粉降解酶的情况下才表现出明显的稳定性，从而被激活。酯键连接的淀粉-米非司酮缀合物在 SIM 中表现出酶响应的激活和释放。
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