Journal article
Imaging therapeutic peptide transport across intestinal barriers
Department of Health Technology, Technical University of Denmark1
Nanofluidics and Bioimaging, NanoBio Light-Systems, Department of Health Technology, Technical University of Denmark2
Stochastic Systems and Signals, NanoBio Light-Systems, Department of Health Technology, Technical University of Denmark3
Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark4
Biomimetics, Department of Health Technology, Technical University of Denmark5
Polymer Cell, Biomimetics, Department of Health Technology, Technical University of Denmark6
Colloids & Biological Interfaces, Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark7
Biologically Inspired Material Engineering, Biomimetics, Department of Health Technology, Technical University of Denmark8
Ocular Drug Delivery, Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark9
Technical University of Denmark10
NanoBio Light-Systems, Department of Health Technology, Technical University of Denmark11
...and 1 moreOral 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.
This journal is
Language: | English |
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Publisher: | RSC |
Year: | 2021 |
Pages: | 1115-1143 |
ISSN: | 26330679 |
Types: | Journal article |
DOI: | 10.1039/d1cb00024a |
ORCIDs: | Larsen, Jannik Bruun , Taebnia, Nayere , Kristensen, Kasper , Mortensen, Kim I. , Flyvbjerg, Henrik , Dolatshahi-Pirouz, Alireza , Larsen, Nanna Wichmann , Larsen, Niels Bent , Marie, Rodolphe , Mündler, Ann Kathrin , Urquhart, Andrew James and Andresen, Thomas Lars |