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Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles
Targeted delivery of drugs is required to efficiently treat intestinal diseases such as colon cancer and inflammation. Nanoparticles could overcome challenges in oral administration caused by drug degradation at low pH and poor permeability through mucus layers, and offer targeted delivery to diseas...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725644/ https://www.ncbi.nlm.nih.gov/pubmed/26855569 http://dx.doi.org/10.2147/IJN.S94013 |
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author | Desai, Diti Prabhakar, Neeraj Mamaeva, Veronika Karaman, Didem Şen Lähdeniemi, Iris AK Sahlgren, Cecilia Rosenholm, Jessica M Toivola, Diana M |
author_facet | Desai, Diti Prabhakar, Neeraj Mamaeva, Veronika Karaman, Didem Şen Lähdeniemi, Iris AK Sahlgren, Cecilia Rosenholm, Jessica M Toivola, Diana M |
author_sort | Desai, Diti |
collection | PubMed |
description | Targeted delivery of drugs is required to efficiently treat intestinal diseases such as colon cancer and inflammation. Nanoparticles could overcome challenges in oral administration caused by drug degradation at low pH and poor permeability through mucus layers, and offer targeted delivery to diseased cells in order to avoid adverse effects. Here, we demonstrate that functionalization of mesoporous silica nanoparticles (MSNs) by polymeric surface grafts facilitates transport through the mucosal barrier and enhances cellular internalization. MSNs functionalized with poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and the targeting ligand folic acid in different combinations are internalized by epithelial cells in vitro and in vivo after oral gavage. Functionalized MSNs loaded with γ-secretase inhibitors of the Notch pathway, a key regulator of intestinal progenitor cells, colon cancer, and inflammation, demonstrated enhanced intestinal goblet cell differentiation as compared to free drug. Drug-loaded MSNs thus remained intact in vivo, further confirmed by exposure to simulated gastric and intestinal fluids in vitro. Drug targeting and efficacy in different parts of the intestine could be tuned by MSN surface modifications, with PEI coating exhibiting higher affinity for the small intestine and PEI–PEG coating for the colon. The data highlight the potential of nanomedicines for targeted delivery to distinct regions of the tissue for strict therapeutic control. |
format | Online Article Text |
id | pubmed-4725644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47256442016-02-05 Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles Desai, Diti Prabhakar, Neeraj Mamaeva, Veronika Karaman, Didem Şen Lähdeniemi, Iris AK Sahlgren, Cecilia Rosenholm, Jessica M Toivola, Diana M Int J Nanomedicine Original Research Targeted delivery of drugs is required to efficiently treat intestinal diseases such as colon cancer and inflammation. Nanoparticles could overcome challenges in oral administration caused by drug degradation at low pH and poor permeability through mucus layers, and offer targeted delivery to diseased cells in order to avoid adverse effects. Here, we demonstrate that functionalization of mesoporous silica nanoparticles (MSNs) by polymeric surface grafts facilitates transport through the mucosal barrier and enhances cellular internalization. MSNs functionalized with poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and the targeting ligand folic acid in different combinations are internalized by epithelial cells in vitro and in vivo after oral gavage. Functionalized MSNs loaded with γ-secretase inhibitors of the Notch pathway, a key regulator of intestinal progenitor cells, colon cancer, and inflammation, demonstrated enhanced intestinal goblet cell differentiation as compared to free drug. Drug-loaded MSNs thus remained intact in vivo, further confirmed by exposure to simulated gastric and intestinal fluids in vitro. Drug targeting and efficacy in different parts of the intestine could be tuned by MSN surface modifications, with PEI coating exhibiting higher affinity for the small intestine and PEI–PEG coating for the colon. The data highlight the potential of nanomedicines for targeted delivery to distinct regions of the tissue for strict therapeutic control. Dove Medical Press 2016-01-18 /pmc/articles/PMC4725644/ /pubmed/26855569 http://dx.doi.org/10.2147/IJN.S94013 Text en © 2016 Desai et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Desai, Diti Prabhakar, Neeraj Mamaeva, Veronika Karaman, Didem Şen Lähdeniemi, Iris AK Sahlgren, Cecilia Rosenholm, Jessica M Toivola, Diana M Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles |
title | Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles |
title_full | Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles |
title_fullStr | Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles |
title_full_unstemmed | Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles |
title_short | Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles |
title_sort | targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently peg-pei functionalized mesoporous silica nanoparticles |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725644/ https://www.ncbi.nlm.nih.gov/pubmed/26855569 http://dx.doi.org/10.2147/IJN.S94013 |
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