Mechanisms of uptake and transport of particulate formulations in the small intestine
Date
2022
Authors
Delon, L.
Gibson, R.J.
Prestidge, C.A.
Thierry, B.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Controlled Release, 2022; 343:584-599
Statement of Responsibility
Ludivine Delon, Rachel J.Gibson, Clive A. Prestidge, Benjamin Thierry
Conference Name
Abstract
Micro- and nano-scale particulate formulations are widely investigated towards improving the oral bioavail- ability of both biologics and drugs with low solubility and/or low intestinal permeability. Particulate formula- tions harnessing physiological intestinal transport pathways have recently yielded remarkably high oral bioavailabilities, illustrating the need for better understanding the specific pathways underpinning particle small intestinal absorption and the relative role of intestinal cells. Mechanistic knowledge has been hampered by the well acknowledged limitations of current in vitro, in vivo and ex vivo models relevant to the human intestinal physiology and the lack of standardization in studies reporting absorption data. Here we review the relevant literature and critically discusses absorption pathways with a focus on the role of specific intestinal epithelial and immune cells. We conclude that while Microfold (M) cells are a valid target for oral vaccines, enterocytes play a greater role in the systemic bioavailability of orally administrated particulate formulations, particularly within the sub-micron size range. We also comment on less-reported mechanisms such as paracellular permeability of particles, persorption due to cell damage and uptake by migratory immune cells.
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Data source: Supplementary data, https://doi.org/10.1016/j.jconrel.2022.02.006
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© 2022 Elsevier B.V. All rights reserved.