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Drug Transporters and Their Role in Absorption and Disposition of Peptides and Peptide-Based Pharmaceuticals

par Lindley, David D.J.;Carl, Stephen M;Herrera-Ruiz, Dea;Pan, Li L.F.;Ward, Lori;Goole, Jonathan ;Gudmundsson, Olafur;Behymer, Matthew;Knipp, Gregory Thomas
Référence Oral Bioavailability and Drug Delivery: From Basics to Advanced Concepts and Applications, wiley, page (393-415)
Publication Publié, 2023-01

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Résumé :

Aberrations in critical protein-protein interactions often serve as the underlying cause in the pathogenesis of diseases and disorders. The continuous discovery and development of peptide- and protein-based therapeutics aimed at mitigating these diseases and disorders has been the focus of the pharmaceutical field for decades. The field dates back to the therapeutic utility of porcine insulin in 1922. Technological advances in the field since then, including recombinant technologies, novel chemical synthetic strategies, and more recent advances like peptide stapling, have dramatically increased the therapeutic potential of peptides and proteins. Traditionally, the delivery of larger peptides and proteins was limited to parenteral products, which can limit patient compliance when compared to peroral delivery. Moreover, smaller peptide-based therapies have demonstrated poor bioavailability when delivered orally. Here, we highlight some of the advances that have been made to increase the absorption and disposition of peptide-based agents when delivered via the peroral route. We will discuss factors that may influence epithelial absorption through different routes of permeation; such factors need to be considered by investigators to enhance small molecule peptide-based absorption and distribution during discovery with the ultimate goal of translation to the clinic.