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

Shubber S, Vllasaliu D, Rauch C, Jordan F, Illum L, Stolnik S - Pharm. Res. (2014)

Bottom Line: The rate of cell endocytosis was measured in vitro in the presence of Solutol® HS15 using a membrane probe, FM 2-10.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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Drug Delivery and Tissue Engineering, School of Pharmacy Boots Science Building, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.

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.

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Normalisation of pyrene emission peaks 1:3 to determine the CMC of Solutol® HS15 in deionised water, HBSS:HEPES (25 mM) and PBS (162.7 mM). Profiles for 2 μM final pyrene solution are shown. Normalised values presented as mean values ± SD of N = 3, n = 4.
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Fig2: Normalisation of pyrene emission peaks 1:3 to determine the CMC of Solutol® HS15 in deionised water, HBSS:HEPES (25 mM) and PBS (162.7 mM). Profiles for 2 μM final pyrene solution are shown. Normalised values presented as mean values ± SD of N = 3, n = 4.

Mentions: The critical micellar concentration (CMC) of Solutol® HS15 in biologically relevant aqueous media was determined using the pyrene 1:3 normalisation assay, typically used in the field to confirm the CMC of surfactants (16, 17). Fig. 2 illustrates the CMC of Solutol® HS15 in deionised water, PBS (167 mM), as well as in HBSS:HEPES (25 mM), which was subsequently used for cell studies. The CMC values reside in the concentration range of 0.06 and 0.1 mM Solutol® HS15 for all media used.Fig. 2


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

Shubber S, Vllasaliu D, Rauch C, Jordan F, Illum L, Stolnik S - Pharm. Res. (2014)

Normalisation of pyrene emission peaks 1:3 to determine the CMC of Solutol® HS15 in deionised water, HBSS:HEPES (25 mM) and PBS (162.7 mM). Profiles for 2 μM final pyrene solution are shown. Normalised values presented as mean values ± SD of N = 3, n = 4.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4300420&req=5

Fig2: Normalisation of pyrene emission peaks 1:3 to determine the CMC of Solutol® HS15 in deionised water, HBSS:HEPES (25 mM) and PBS (162.7 mM). Profiles for 2 μM final pyrene solution are shown. Normalised values presented as mean values ± SD of N = 3, n = 4.
Mentions: The critical micellar concentration (CMC) of Solutol® HS15 in biologically relevant aqueous media was determined using the pyrene 1:3 normalisation assay, typically used in the field to confirm the CMC of surfactants (16, 17). Fig. 2 illustrates the CMC of Solutol® HS15 in deionised water, PBS (167 mM), as well as in HBSS:HEPES (25 mM), which was subsequently used for cell studies. The CMC values reside in the concentration range of 0.06 and 0.1 mM Solutol® HS15 for all media used.Fig. 2

Bottom Line: The rate of cell endocytosis was measured in vitro in the presence of Solutol® HS15 using a membrane probe, FM 2-10.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.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Drug Delivery and Tissue Engineering, School of Pharmacy Boots Science Building, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.

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.

Show MeSH