Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated In Vitro in cell cultures.

Shubber, Saif and Vllasaliu, Driton and Rauch, Cyril and Jordan, Faron and Illum, Lisbeth and Stolnik, Snjezana (2015) Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated In Vitro in cell cultures. Pharmaceutical Research, 32 (2). pp. 516-527. ISSN 0724-8741

Full content URL: http://link.springer.com/article/10.1007%2Fs11095-...

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Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated In Vitro in cell cultures
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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.

Keywords:absorption enhancers, Calu-3 cells, Mucosal protein delivery, Solutol® HS15, Surfactants, JCOpen
Subjects:B Subjects allied to Medicine > B200 Pharmacology, Toxicology and Pharmacy
Divisions:College of Science > School of Pharmacy
ID Code:14838
Deposited On:09 Sep 2014 15:30

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