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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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Principle component of CriticalSorb™ (Critical Pharmaceuticals, Nottingham, UK), Solutol ® HS15; a mixture of Polyglycol mono- and di-esters of 12 hydroxystearic acid. Taken from (21).
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Related In: Results  -  Collection


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Fig1: Principle component of CriticalSorb™ (Critical Pharmaceuticals, Nottingham, UK), Solutol ® HS15; a mixture of Polyglycol mono- and di-esters of 12 hydroxystearic acid. Taken from (21).

Mentions: CriticalSorb® is a novel absorption enhancing formulation that contains Macrogol 15 hydroxy stearate (Solutol® HS15) (Fig. 1) as the principal component, proposed to act as a permeability enhancer. CriticalSorb® technology is currently in early clinical development stage as a nasal spray formulation for delivery of human growth hormone, based on a previously demonstrated enhancement of the bioavailability of human growth hormone and insulin in both animal studies and human trials (8). In addition, Solutol® HS15 is currently used to increase the aqueous solubility of Biopharmaceutical Classification System (BCS) Class 2 and 4 lipophilic molecules (9).Fig. 1


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)

Principle component of CriticalSorb™ (Critical Pharmaceuticals, Nottingham, UK), Solutol ® HS15; a mixture of Polyglycol mono- and di-esters of 12 hydroxystearic acid. Taken from (21).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Principle component of CriticalSorb™ (Critical Pharmaceuticals, Nottingham, UK), Solutol ® HS15; a mixture of Polyglycol mono- and di-esters of 12 hydroxystearic acid. Taken from (21).
Mentions: CriticalSorb® is a novel absorption enhancing formulation that contains Macrogol 15 hydroxy stearate (Solutol® HS15) (Fig. 1) as the principal component, proposed to act as a permeability enhancer. CriticalSorb® technology is currently in early clinical development stage as a nasal spray formulation for delivery of human growth hormone, based on a previously demonstrated enhancement of the bioavailability of human growth hormone and insulin in both animal studies and human trials (8). In addition, Solutol® HS15 is currently used to increase the aqueous solubility of Biopharmaceutical Classification System (BCS) Class 2 and 4 lipophilic molecules (9).Fig. 1

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