Colon-Specific Delivery of Probenecid Enhances Therapeutic Activity of the Uricosuric Agent Against Rat Colitis.

ABSTRACT: Background/Objectives: Probenecid (PBN) is a uricosuric agent that facilitates the excretion of uric acid and is used to treat gout. Here, a colon-targeted prodrug of PBN was designed to facilitate repositioning as a treatment for inflammatory bowel disease (IBD). Methods: The carboxylic group in PBN was amide-conjugated with the amine groups of acidic amino acids to yield aspartic acid-conjugated PBN (PBN-AA) and glutamic acid-conjugated PBN (PBN-GA). Conjugation with amino acids increased the hydrophilicity of PBN and decreased cell permeability across the Caco-2 cell monolayer. While remaining intact in buffers (pH 1.2, 6.8) and in the small intestinal contents of rats, the conjugates were cleaved to release PBN from the cecal contents of rats, with a significant differenc

SUBMITTER: Jeong Y 

PROVIDER: S-EPMC12655446 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature