A novel oral prodrug-targeting transporter MCT 1: 5-fluorouracil-dicarboxylate monoester conjugates.

ABSTRACT: Monocarboxylate transporter 1 (MCT1) is responsible for oral absorption of short-chain monocarboxylic acids from small intestine, hence, it's likely to serve as an ideal design target for the development of oral prodrugs. However, potential application of MCT1 to facilitate the oral delivery is still unclear. Irregular oral absorption, poor permeability and bioavailability greatly limit the oral delivery efficiency of 5-fluorouracil (5-FU). Herein, we design three 5-FU-fatty acid conjugates targeting intestinal MCT1 with different lipophilic linkages. Interestingly, due to high MCT1 affinity and good gastrointestinal stability, 5-FU-octanedioic acid monoester prodrug exhibited significant improvement in membrane permeability (13.1-fold) and oral bioavailability (4.1-fold) compared to 5-FU.

SUBMITTER: Sun Y 

PROVIDER: S-EPMC7032090 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature