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Intestinal permeation enhancers to improve oral bioavailability of macromolecules: reasons for low efficacy in humans

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journal contribution
posted on 04.08.2021, 13:46 by Sam MaherSam Maher, Caroline GeogheganCaroline Geoghegan, David J Brayden

Introduction: Intestinal permeation enhancers (PEs) are substances that transiently alter the intestinal epithelial barrier to facilitate permeation of macromolecules with low oral bioavailability (BA). While a number of PEs have progressed to clinical testing in conventional formulations with macromolecules, there has been only low single digit increases in oral BA, irrespective of whether the drug met primary or secondary clinical endpoints.

Areas covered: This article considers the causes of sub-optimal BA of macromolecules from PE dosage forms and suggests approaches that may improve performance in humans.

Expert opinion: Permeation enhancement is most effective when the PE is co-localized with the macromolecule at the epithelial surface. Conditions in the GI tract impede optimal co-localization. Novel delivery systems that limit dilution and spreading of the PE and macromolecule in the small intestine have attempted to replicate promising enhancement efficacy observed in static drug delivery models.

Funding

Science Foundation Ireland (SFI) CÚRAM Centre for Medical Devices, grant number 13/RC/2073

SFI BiOrbic Centre for Bioeconomy, grant number 16/RC/3889

EU Regional Development Fund

History

Comments

This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Drug Delivery on 29 September 2020 available online: http://www.tandfonline.com/ DOI: https://doi.org/10.1080/17425247.2021.1825375

Published Citation

Maher S, Geoghegan C, Brayden DJ. Intestinal permeation enhancers to improve oral bioavailability of macromolecules: reasons for low efficacy in humans. Expert Opin Drug Deliv. 2021;18(2):273-300.

Publication Date

29 September 2020

PubMed ID

32937089

Department/Unit

  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Chemistry and Pharmaceutical Sciences

Publisher

Informa UK Limited

Version

  • Accepted Version (Postprint)