Imaging therapeutic peptide transport across intestinal barriers.

Autor:	Larsen JB; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Taebnia N; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Dolatshahi-Pirouz A; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Eriksen AZ; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Hjørringgaard C; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Kristensen K; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Larsen NW; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Larsen NB; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Marie R; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Mündler AK; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Parhamifar L; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Urquhart AJ; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Weller A; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Mortensen KI; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Flyvbjerg H; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk., Andresen TL; Center for Intestinal Absorption and Transport of Biopharmaceuticals, Department of Health Technology, Technical University of Denmark DK-2800, Kgs. Lyngby Denmark tlan@dtu.dk.
Jazyk:	angličtina
Zdroj:	RSC chemical biology [RSC Chem Biol] 2021 Jun 15; Vol. 2 (4), pp. 1115-1143. Date of Electronic Publication: 2021 Jun 15 (Print Publication: 2021).
DOI:	10.1039/d1cb00024a
Abstrakt:	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. Competing Interests: None. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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