TY - JOUR
T1 - Imaging therapeutic peptide transport across intestinal barriers
AU - Larsen, Jannik Bruun
AU - Taebnia, Nayere
AU - Dolatshahi-Pirouz, Alireza
AU - Eriksen, Anne Zebitz
AU - Hjørringgaard, Claudia
AU - Kristensen, Kasper
AU - Larsen, Nanna Wichmann
AU - Larsen, Niels Bent
AU - Marie, Rodolphe
AU - Mündler, Ann Kathrin
AU - Parhamifar, Ladan
AU - Urquhart, Andrew James
AU - Weller, Arjen
AU - Mortensen, Kim I.
AU - Flyvbjerg, Henrik
AU - Andresen, Thomas Lars
N1 - Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2021
Y1 - 2021
N2 - 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. This journal is
AB - 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. This journal is
U2 - 10.1039/d1cb00024a
DO - 10.1039/d1cb00024a
M3 - Journal article
C2 - 34458827
AN - SCOPUS:85112166684
SN - 2633-0679
VL - 2
SP - 1115
EP - 1143
JO - RSC Chemical Biology
JF - RSC Chemical Biology
IS - 4
ER -