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INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH

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Published by : Advanced Scientific Research
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0975-2366
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IJPR 9[3] July - September 2017 Special Issue

July - September 9[3] 2017

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Semisynthetic colon-specific prodrugs of boswellic acid for inflammatory bowel disease: Design, Pharmacokinetic and Pharmacodynamic studies

Author: AJINKYA SARKATE, SUNEELA S. DHANESHWAR
Abstract: Mutual amide prodrugs of ?-boswellic acid (BBA) with L-glutamine and L-cysteine were synthesized for the management of inflammatory bowel disease. Conjugation with amino acids improved the hydrophilicity of BBA (log P: 4.9 to5.3) to enable efficient delivery to colon. Prodrugs were stable in 0.05M HCl buffer (pH 1.2) and stomach homogenates. Negligible hydrolysis was observed in phosphate buffer and intestinal homogenates. Prodrugs were substantially cleaved to release BBA in homogenates of colon (59-63%) and rat fecal matter (49-52%). Site-specifically enhanced bioavailability of BBA could be achieved in colon and prodrug of BBA with L-glutamine (BG) demonstrated a significant ameliorating effect on the inflamed colonic mucosa in TNBS-induced colitis in Wistar rats without the SLZ-associated adversities on stomach, liver and pancreas. BG could be developed further as a safer colon-specific prodrug for potential application in the management of IBD.
Keyword: Inflammatory bowel disease, Complementary and alternative medicine, Boswellic acid, colon-targeting, mutual prodrugs, TNBS-induced colitis
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