Investigation of mitigating effect of colon-specific prodrugs of boswellic acid on 2,4,6-trinitrobenzene sulfonic acidinduced colitis in Wistar rats: Design, kinetics and biological evaluation

作     者：Ajinkya Sarkate Suneela S Dhaneshwar 

作者机构：Department of Pharmaceutical ChemistryPoona College of PharmacyBharati Vidyapeeth UniversityMaharashtra 411038India 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2017年第23卷第7期

页      面：1147-1162页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 10[医学] 

主　　题：煽动性的肠疾病 Boswellic 酸 互补、其他的药 指向冒号 相互的 prodrugs 氨基酸 导致 TNBS 的大肠炎 

摘      要：AIM To develop a colon-targeting bioreversible delivery system for β-boswellic acid(BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced colitis in rats.METHODS Synthesis of 4 co-drugs of BBA with essential amino acids was achieved by CDI coupling, followed by their spectral characterization. In vitro kinetics were studied by HPLC in aqueous buffers, homogenates of gastrointestinal tract and fecal matter. In vivo kinetic studies were performed in Wistar rat plasma, urine and feces. The prodrugs were screened in TNBS-induced colitis modeled Wistar rats. Statistical significance was assumed at P 0.05, P 0.01, P 0.001 when compared with disease controls using one-way and two-way ANOVAs.RESULTS Prodrugs were stable in 0.05 mol/L HCl buffer(p H 1.2) and stomach homogenates. Negligible hydrolysis was observed in phosphate buffer and intestinal homogenates. Substantial release(55%-72% and 68%-86%) of BBA was achieved in rat fecal matter and homogenates of colon. In vivo studies of BBA with L-tryptophan(BT) authenticated colon-specific release of BBA. But, surprisingly substantial concentration of BBA was seen to reach the systemic circulation due to probable absorption through colonic mucosa. Sitespecifically enhanced bioavailability of BBA could be achieved in colon, which resulted in demonstration of significant mitigating effect on TNBS-induced colitis in rats without inducing any adverse effects on stomach, liver and pancreas. Prodrug of BT was found to be 1.7%(P 0.001) superior than sulfasalazine in reducing the inflammation to colon among all prodrugs tested. CONCLUSION The outcome of this study strongly suggests that these prodrugs might have dual applicability to inflammatory bowel disease and chronotherapy of rheumatoid arthritis.