Saif Shubber
Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated in vitro in cell cultures
Shubber, Saif; Vllasaliu, Driton; Rauch, Cyril; Jordan, Faron; Illum, Lisbeth; Stolnik-Trenkic, Snow
Authors
Driton Vllasaliu
CYRIL RAUCH CYRIL.RAUCH@NOTTINGHAM.AC.UK
Associate Professor
Faron Jordan
Lisbeth Illum
Snow Stolnik-Trenkic
Abstract
Purpose: CriticalSorb™, with the principal component Solutol® HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol® HS15.
Methods: Micelle size and CMC of Solutol® HS15 were determined in biologically relevant media. Polarised airway Calu-3 cell layers were used to measure the permeability of a panel of biological drugs, and to assess changes in TEER, tight junction and F-actin morphology. The rate of cell endocytosis was measured in vitro in the presence of Solutol® HS15 using a membrane probe, FM 2–10.
Results: This work initially confirms surfactant-like behaviour of Solutol® HS15 in aqueous media, while subsequent experiments demonstrate that the effect of Solutol® HS15 on epithelial tight junctions is different from a ‘classical’ tight junction opening agent and illustrate the effect of Solutol® HS15 on the cell membrane (endocytosis rate) and F-actin cytoskeleton.
Conclusion: Solutol® HS15 is the principle component of CriticalSorb™ that has shown an enhancement in permeability of medium sized biological drugs across epithelia. This study suggests that its mechanism of action arises primarily from effects on the cell membrane and consequent impacts on the cell cytoskeleton in terms of actin organisation and tight junction opening.
Journal Article Type | Article |
---|---|
Acceptance Date | Aug 15, 2014 |
Online Publication Date | Sep 5, 2014 |
Publication Date | Feb 1, 2015 |
Deposit Date | Oct 3, 2017 |
Publicly Available Date | Feb 25, 2019 |
Print ISSN | 0724-8741 |
Electronic ISSN | 1573-904X |
Publisher | American Association of Pharmaceutical Scientists |
Peer Reviewed | Peer Reviewed |
Volume | 32 |
Issue | 2 |
Pages | 516-527 |
DOI | https://doi.org/10.1007/s11095-014-1481-5 |
Public URL | https://nottingham-repository.worktribe.com/output/1101812 |
Publisher URL | https://link.springer.com/article/10.1007%2Fs11095-014-1481-5 |
PMID | 25190006 |
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Mechanism of Mucosal Permeability Enhancement of CriticalSorb® (Solutol® HS15) Investigated In Vitro in Cell Cultures
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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