Advances in biotechnology have provided a wide range of therapeutically active and commercially available biologic large molecules as protein and peptide drugs. However, oral administration of these drugs has been highly limited due to the stability and the difficulties to cross the gastrointestinal membrane. Significant research attempts have been made in recent years to utilize carrier-mediated transport systems for enhancement in the oral bioavailability. Among various intestinal transporters, the intestinal bile acid transporter has a good potential because of its higher capacity and low structural selectivity. The transport system facilitates the daily absorption of 10-20 g bile salts at a more than 95% efficiency rate.
The system also tolerates significant chemical modifications at the C3 and C24 positions of the sterol nucleus. Thus, the intestinal bile acid transporter has been specifically investigated for its ability to increase the oral absorption of cholic acid conjugates of proteins and small peptides through the carrier-mediated transport mechanism. The fact that the bile acid transporter tolerates the chemical modifications of cholic acid provides a solid rationale for the development of a cholic acid-peptide conjugate for enhanced oral absorption.
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