Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC)

Research output: Contribution to journalJournal articlepeer-review

Standard

Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC). / Mortensen, J. S.; Bohr, S. S.R.; Harloff-Helleberg, S.; Hatzakis, N. S.; Saaby, L.; Nielsen, H. M.

In: Journal of Controlled Release, Vol. 352, 2022, p. 163-178.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Mortensen, JS, Bohr, SSR, Harloff-Helleberg, S, Hatzakis, NS, Saaby, L & Nielsen, HM 2022, 'Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC)', Journal of Controlled Release, vol. 352, pp. 163-178. https://doi.org/10.1016/j.jconrel.2022.09.034

APA

Mortensen, J. S., Bohr, S. S. R., Harloff-Helleberg, S., Hatzakis, N. S., Saaby, L., & Nielsen, H. M. (2022). Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC). Journal of Controlled Release, 352, 163-178. https://doi.org/10.1016/j.jconrel.2022.09.034

Vancouver

Mortensen JS, Bohr SSR, Harloff-Helleberg S, Hatzakis NS, Saaby L, Nielsen HM. Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC). Journal of Controlled Release. 2022;352:163-178. https://doi.org/10.1016/j.jconrel.2022.09.034

Author

Mortensen, J. S. ; Bohr, S. S.R. ; Harloff-Helleberg, S. ; Hatzakis, N. S. ; Saaby, L. ; Nielsen, H. M. / Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC). In: Journal of Controlled Release. 2022 ; Vol. 352. pp. 163-178.

Bibtex

@article{24bd0835ee024c3eaf9060161df5f49d,
title = "Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC)",
abstract = "Drug delivery systems (DDS) for oral delivery of peptide drugs contain excipients that facilitate and enhance absorption. However, little knowledge exists on how DDS excipients such as permeation enhancers interact with the gastrointestinal mucus barrier. This study aimed to investigate interactions of the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC) with ex vivo porcine intestinal mucus (PIM), ex vivo porcine gastric mucus (PGM), as well as with in vitro biosimilar mucus (BM) by profiling their physical and barrier properties upon exposure to SNAC. Bulk mucus permeability studies using the peptides cyclosporine A and vancomycin, ovalbumin as a model protein, as well as fluorescein-isothiocyanate dextrans (FDs) of different molecular weights and different surface charges were conducted in parallel to mucus retention force studies using a texture analyzer, rheological studies, cryo-scanning electron microscopy (cryo-SEM), and single particle tracking of fluorescence-labelled nanoparticles to investigate the effects of the SNAC-mucus interaction. The exposure of SNAC to PIM increased the mucus retention force, storage modulus, viscosity, increased nanoparticle confinement within PIM as well as decreased the permeation of cyclosporine A and ovalbumin through PIM. Surprisingly, the viscosity of PGM and the permeation of cyclosporine A and ovalbumin through PGM was unaffected by the presence of SNAC, thus the effect of SNAC depended on the regional site that mucus was collected from. In the absence of SNAC, the permeation of different molecular weight and differently charged FDs through PIM was comparable to that through BM. However, while bulk permeation of neither of the FDs through PIM was affected by SNAC, the presence of SNAC decreased the permeation of FD4 and increased the permeation of FD150 kDa through BM. Additionally, and in contrast to observations in PIM, nanoparticle confinement within BM remained unaffected by the presence of SNAC. In conclusion, the present study showed that SNAC altered the physical and barrier properties of PIM, but not of PGM. The effects of SNAC in PIM were not observed in the BM in vitro model. Altogether, the study highlights the need for further understanding how permeation enhancers influence the mucus barrier and illustrates that the selected mucus model for such studies should be chosen with care.",
keywords = "Ex vivo porcine gastric mucus, Ex vivo porcine intestinal mucus, Mucus retention force, Permeability, Permeation enhancer, Rheology, Salcaprozate sodium, Single particle tracking",
author = "Mortensen, {J. S.} and Bohr, {S. S.R.} and S. Harloff-Helleberg and Hatzakis, {N. S.} and L. Saaby and Nielsen, {H. M.}",
note = "Funding Information: The Department of Experimental Medicine (University of Copenhagen, UCPH) are greatly acknowledged for providing pig intestines. Laboratory technician Karina Vissing, scholar student Sylvester Petersen and Master student Lasse Krog (Department of Pharmacy, UCPH) are acknowledged for their help with mucus collection. The Novo Nordisk Foundation is acknowledged for funding the project (Grand Challenge Program NNF16OC0021948 through the Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), UCPH). Additionally, this work was supported by the Lundbeck Foundation (project no. R303-2018-2968 ). Further, the Innovative Medicines Initiative Joint Undertaking ( European Union's Seventh Framework program FP7/2007-2013 and EFPIA: 115363 ) and the Carlsberg Foundation are acknowledged for support. Funding Information: The Department of Experimental Medicine (University of Copenhagen, UCPH) are greatly acknowledged for providing pig intestines. Laboratory technician Karina Vissing, scholar student Sylvester Petersen and Master student Lasse Krog (Department of Pharmacy, UCPH) are acknowledged for their help with mucus collection. The Novo Nordisk Foundation is acknowledged for funding the project (Grand Challenge Program NNF16OC0021948 through the Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), UCPH). Additionally, this work was supported by the Lundbeck Foundation (project no. R303-2018-2968). Further, the Innovative Medicines Initiative Joint Undertaking (European Union's Seventh Framework program FP7/2007-2013 and EFPIA: 115363) and the Carlsberg Foundation are acknowledged for support. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
doi = "10.1016/j.jconrel.2022.09.034",
language = "English",
volume = "352",
pages = "163--178",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC)

AU - Mortensen, J. S.

AU - Bohr, S. S.R.

AU - Harloff-Helleberg, S.

AU - Hatzakis, N. S.

AU - Saaby, L.

AU - Nielsen, H. M.

N1 - Funding Information: The Department of Experimental Medicine (University of Copenhagen, UCPH) are greatly acknowledged for providing pig intestines. Laboratory technician Karina Vissing, scholar student Sylvester Petersen and Master student Lasse Krog (Department of Pharmacy, UCPH) are acknowledged for their help with mucus collection. The Novo Nordisk Foundation is acknowledged for funding the project (Grand Challenge Program NNF16OC0021948 through the Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), UCPH). Additionally, this work was supported by the Lundbeck Foundation (project no. R303-2018-2968 ). Further, the Innovative Medicines Initiative Joint Undertaking ( European Union's Seventh Framework program FP7/2007-2013 and EFPIA: 115363 ) and the Carlsberg Foundation are acknowledged for support. Funding Information: The Department of Experimental Medicine (University of Copenhagen, UCPH) are greatly acknowledged for providing pig intestines. Laboratory technician Karina Vissing, scholar student Sylvester Petersen and Master student Lasse Krog (Department of Pharmacy, UCPH) are acknowledged for their help with mucus collection. The Novo Nordisk Foundation is acknowledged for funding the project (Grand Challenge Program NNF16OC0021948 through the Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), UCPH). Additionally, this work was supported by the Lundbeck Foundation (project no. R303-2018-2968). Further, the Innovative Medicines Initiative Joint Undertaking (European Union's Seventh Framework program FP7/2007-2013 and EFPIA: 115363) and the Carlsberg Foundation are acknowledged for support. Publisher Copyright: © 2022 The Authors

PY - 2022

Y1 - 2022

N2 - Drug delivery systems (DDS) for oral delivery of peptide drugs contain excipients that facilitate and enhance absorption. However, little knowledge exists on how DDS excipients such as permeation enhancers interact with the gastrointestinal mucus barrier. This study aimed to investigate interactions of the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC) with ex vivo porcine intestinal mucus (PIM), ex vivo porcine gastric mucus (PGM), as well as with in vitro biosimilar mucus (BM) by profiling their physical and barrier properties upon exposure to SNAC. Bulk mucus permeability studies using the peptides cyclosporine A and vancomycin, ovalbumin as a model protein, as well as fluorescein-isothiocyanate dextrans (FDs) of different molecular weights and different surface charges were conducted in parallel to mucus retention force studies using a texture analyzer, rheological studies, cryo-scanning electron microscopy (cryo-SEM), and single particle tracking of fluorescence-labelled nanoparticles to investigate the effects of the SNAC-mucus interaction. The exposure of SNAC to PIM increased the mucus retention force, storage modulus, viscosity, increased nanoparticle confinement within PIM as well as decreased the permeation of cyclosporine A and ovalbumin through PIM. Surprisingly, the viscosity of PGM and the permeation of cyclosporine A and ovalbumin through PGM was unaffected by the presence of SNAC, thus the effect of SNAC depended on the regional site that mucus was collected from. In the absence of SNAC, the permeation of different molecular weight and differently charged FDs through PIM was comparable to that through BM. However, while bulk permeation of neither of the FDs through PIM was affected by SNAC, the presence of SNAC decreased the permeation of FD4 and increased the permeation of FD150 kDa through BM. Additionally, and in contrast to observations in PIM, nanoparticle confinement within BM remained unaffected by the presence of SNAC. In conclusion, the present study showed that SNAC altered the physical and barrier properties of PIM, but not of PGM. The effects of SNAC in PIM were not observed in the BM in vitro model. Altogether, the study highlights the need for further understanding how permeation enhancers influence the mucus barrier and illustrates that the selected mucus model for such studies should be chosen with care.

AB - Drug delivery systems (DDS) for oral delivery of peptide drugs contain excipients that facilitate and enhance absorption. However, little knowledge exists on how DDS excipients such as permeation enhancers interact with the gastrointestinal mucus barrier. This study aimed to investigate interactions of the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC) with ex vivo porcine intestinal mucus (PIM), ex vivo porcine gastric mucus (PGM), as well as with in vitro biosimilar mucus (BM) by profiling their physical and barrier properties upon exposure to SNAC. Bulk mucus permeability studies using the peptides cyclosporine A and vancomycin, ovalbumin as a model protein, as well as fluorescein-isothiocyanate dextrans (FDs) of different molecular weights and different surface charges were conducted in parallel to mucus retention force studies using a texture analyzer, rheological studies, cryo-scanning electron microscopy (cryo-SEM), and single particle tracking of fluorescence-labelled nanoparticles to investigate the effects of the SNAC-mucus interaction. The exposure of SNAC to PIM increased the mucus retention force, storage modulus, viscosity, increased nanoparticle confinement within PIM as well as decreased the permeation of cyclosporine A and ovalbumin through PIM. Surprisingly, the viscosity of PGM and the permeation of cyclosporine A and ovalbumin through PGM was unaffected by the presence of SNAC, thus the effect of SNAC depended on the regional site that mucus was collected from. In the absence of SNAC, the permeation of different molecular weight and differently charged FDs through PIM was comparable to that through BM. However, while bulk permeation of neither of the FDs through PIM was affected by SNAC, the presence of SNAC decreased the permeation of FD4 and increased the permeation of FD150 kDa through BM. Additionally, and in contrast to observations in PIM, nanoparticle confinement within BM remained unaffected by the presence of SNAC. In conclusion, the present study showed that SNAC altered the physical and barrier properties of PIM, but not of PGM. The effects of SNAC in PIM were not observed in the BM in vitro model. Altogether, the study highlights the need for further understanding how permeation enhancers influence the mucus barrier and illustrates that the selected mucus model for such studies should be chosen with care.

KW - Ex vivo porcine gastric mucus

KW - Ex vivo porcine intestinal mucus

KW - Mucus retention force

KW - Permeability

KW - Permeation enhancer

KW - Rheology

KW - Salcaprozate sodium

KW - Single particle tracking

U2 - 10.1016/j.jconrel.2022.09.034

DO - 10.1016/j.jconrel.2022.09.034

M3 - Journal article

C2 - 36314534

AN - SCOPUS:85140139913

VL - 352

SP - 163

EP - 178

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -

ID: 323979398