Issue 4, 2021

Imaging therapeutic peptide transport across intestinal barriers

Abstract

Oral delivery is a highly preferred method for drug administration due to high patient compliance. However, oral administration is intrinsically challenging for pharmacologically interesting drug classes, in particular pharmaceutical peptides, due to the biological barriers associated with the gastrointestinal tract. In this review, we start by summarizing the pharmacological performance of several clinically relevant orally administrated therapeutic peptides, highlighting their low bioavailabilities. Thus, there is a strong need to increase the transport of peptide drugs across the intestinal barrier to realize future treatment needs and further development in the field. Currently, progress is hampered by a lack of understanding of transport mechanisms that govern intestinal absorption and transport of peptide drugs, including the effects of the permeability enhancers commonly used to mediate uptake. We describe how, for the past decades, mechanistic insights have predominantly been gained using functional assays with end-point read-out capabilities, which only allow indirect study of peptide transport mechanisms. We then focus on fluorescence imaging that, on the other hand, provides opportunities to directly visualize and thus follow peptide transport at high spatiotemporal resolution. Consequently, it may provide new and detailed mechanistic understanding of the interplay between the physicochemical properties of peptides and cellular processes; an interplay that determines the efficiency of transport. We review current methodology and state of the art in the field of fluorescence imaging to study intestinal barrier transport of peptides, and provide a comprehensive overview of the imaging-compatible in vitro, ex vivo, and in vivo platforms that currently are being developed to accelerate this emerging field of research.

Graphical abstract: Imaging therapeutic peptide transport across intestinal barriers

Article information

Article type
Review Article
Submitted
04 fev 2021
Accepted
09 iyn 2021
First published
15 iyn 2021
This article is Open Access
Creative Commons BY license

RSC Chem. Biol., 2021,2, 1115-1143

Imaging therapeutic peptide transport across intestinal barriers

J. B. Larsen, N. Taebnia, A. Dolatshahi-Pirouz, A. Z. Eriksen, C. Hjørringgaard, K. Kristensen, N. W. Larsen, N. B. Larsen, R. Marie, A. Mündler, L. Parhamifar, A. J. Urquhart, A. Weller, K. I. Mortensen, H. Flyvbjerg and T. L. Andresen, RSC Chem. Biol., 2021, 2, 1115 DOI: 10.1039/D1CB00024A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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