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Surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model

Besides the many advantages of oral drug administration, challenges like premature drug degradation and limited bioavailability in the gastro-intestinal tract (GIT) remain. A prolonged residence time in the GIT is beneficial for enhancing the therapeutic outcome when treating diseases associated wit...

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Autores principales: Schmid, Roman, Volcic, Meta, Fischer, Stephan, Qu, Zhi, Barth, Holger, Popat, Amirali, Kirchhoff, Frank, Lindén, Mika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10656483/
https://www.ncbi.nlm.nih.gov/pubmed/37978264
http://dx.doi.org/10.1038/s41598-023-47445-6
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author Schmid, Roman
Volcic, Meta
Fischer, Stephan
Qu, Zhi
Barth, Holger
Popat, Amirali
Kirchhoff, Frank
Lindén, Mika
author_facet Schmid, Roman
Volcic, Meta
Fischer, Stephan
Qu, Zhi
Barth, Holger
Popat, Amirali
Kirchhoff, Frank
Lindén, Mika
author_sort Schmid, Roman
collection PubMed
description Besides the many advantages of oral drug administration, challenges like premature drug degradation and limited bioavailability in the gastro-intestinal tract (GIT) remain. A prolonged residence time in the GIT is beneficial for enhancing the therapeutic outcome when treating diseases associated with an increased intestinal clearance rate, like inflammatory bowel disease (IBD). In this study, we synthesized rod-shaped mesoporous silica nanoparticles (MSNs) functionalized with polyethylene glycol (PEG) or hyaluronic acid (HA) and investigated their bio-distribution upon oral administration in vivo. The negatively charged, non-toxic particles showed different accumulation behavior over time in healthy mice and in mice with dextran sulfate sodium (DSS)-induced intestinal inflammation. PEGylated particles were shown to accumulate in the lower intestinal tract of healthy animals, whereas inflammation promoted retention of HA-functionalized particles in this area. Overall systemic absorption was low. However, some particles were detected in organs of mice with DSS-induced colitis, especially in the case of MSN-PEG. The in vivo findings were connected to surface chemistry-related differences in particle adhesion on Caco-2/Raji and mucus-producing Caco-2/Raji/HT29 cell co-culture epithelial models in vitro. While the particle adhesion behavior in vivo was mirrored in the in vitro results, this was not the case for the resorption results, suggesting that the in vitro model does not fully reflect the erosion of the inflamed epithelial tissue. Overall, our study demonstrates the possibility to modulate accumulation and retention of MSNs in the GIT of mice with and without inflammation through surface functionalization, which has important implications for the formulation of nanoparticle-based delivery systems for oral delivery applications.
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spelling pubmed-106564832023-11-17 Surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model Schmid, Roman Volcic, Meta Fischer, Stephan Qu, Zhi Barth, Holger Popat, Amirali Kirchhoff, Frank Lindén, Mika Sci Rep Article Besides the many advantages of oral drug administration, challenges like premature drug degradation and limited bioavailability in the gastro-intestinal tract (GIT) remain. A prolonged residence time in the GIT is beneficial for enhancing the therapeutic outcome when treating diseases associated with an increased intestinal clearance rate, like inflammatory bowel disease (IBD). In this study, we synthesized rod-shaped mesoporous silica nanoparticles (MSNs) functionalized with polyethylene glycol (PEG) or hyaluronic acid (HA) and investigated their bio-distribution upon oral administration in vivo. The negatively charged, non-toxic particles showed different accumulation behavior over time in healthy mice and in mice with dextran sulfate sodium (DSS)-induced intestinal inflammation. PEGylated particles were shown to accumulate in the lower intestinal tract of healthy animals, whereas inflammation promoted retention of HA-functionalized particles in this area. Overall systemic absorption was low. However, some particles were detected in organs of mice with DSS-induced colitis, especially in the case of MSN-PEG. The in vivo findings were connected to surface chemistry-related differences in particle adhesion on Caco-2/Raji and mucus-producing Caco-2/Raji/HT29 cell co-culture epithelial models in vitro. While the particle adhesion behavior in vivo was mirrored in the in vitro results, this was not the case for the resorption results, suggesting that the in vitro model does not fully reflect the erosion of the inflamed epithelial tissue. Overall, our study demonstrates the possibility to modulate accumulation and retention of MSNs in the GIT of mice with and without inflammation through surface functionalization, which has important implications for the formulation of nanoparticle-based delivery systems for oral delivery applications. Nature Publishing Group UK 2023-11-17 /pmc/articles/PMC10656483/ /pubmed/37978264 http://dx.doi.org/10.1038/s41598-023-47445-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Schmid, Roman
Volcic, Meta
Fischer, Stephan
Qu, Zhi
Barth, Holger
Popat, Amirali
Kirchhoff, Frank
Lindén, Mika
Surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model
title Surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model
title_full Surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model
title_fullStr Surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model
title_full_unstemmed Surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model
title_short Surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model
title_sort surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10656483/
https://www.ncbi.nlm.nih.gov/pubmed/37978264
http://dx.doi.org/10.1038/s41598-023-47445-6
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