Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles

Diti Desai,1–4 Neeraj Prabhakar,2 Veronika Mamaeva,3,5 Didem Şen Karaman,2,4 Iris AK Lähdeniemi,1,6 Cecilia Sahlgren,3,7,* Jessica M Rosenholm,2,4,* Diana M Toivola1,6,* 1Cell Biology, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; 2Pharmace...

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Autores principales:	Desai D, Prabhakar N, Mamaeva V, Şen Karaman D, Lähdeniemi IAK, Sahlgren C, Rosenholm JM, Toivola DM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	mesoporous silica intestinal targeting PEG-PEI copolymer oral administration Notch inhibitors Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/92fc998002d34e38a964a3ec3b0d2a59
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spelling	oai:doaj.org-article:92fc998002d34e38a964a3ec3b0d2a592021-12-02T03:58:33ZTargeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles1178-2013https://doaj.org/article/92fc998002d34e38a964a3ec3b0d2a592016-01-01T00:00:00Zhttps://www.dovepress.com/targeted-modulation-of-cell-differentiation-in-distinct-regions-of-the-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Diti Desai,1–4 Neeraj Prabhakar,2 Veronika Mamaeva,3,5 Didem Şen Karaman,2,4 Iris AK Lähdeniemi,1,6 Cecilia Sahlgren,3,7,* Jessica M Rosenholm,2,4,* Diana M Toivola1,6,* 1Cell Biology, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; 2Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; 3Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; 4Laboratory of Physical Chemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; 5Department of Clinical Science, University of Bergen, Bergen, Norway; 6Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland; 7Department of Biomedical Engineering, Technical University of Eindhoven, Eindhoven, the Netherlands *These authors contributed equally to this work Abstract: 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. Keywords: intestinal targeting, PEG-PEI copolymer, Notch inhibitionDesai DPrabhakar NMamaeva VŞen Karaman DLähdeniemi IAKSahlgren CRosenholm JMToivola DMDove Medical Pressarticlemesoporous silicaintestinal targetingPEG-PEI copolymeroral administrationNotch inhibitorsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss Issue 1, Pp 299-313 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	mesoporous silica intestinal targeting PEG-PEI copolymer oral administration Notch inhibitors Medicine (General) R5-920
spellingShingle	mesoporous silica intestinal targeting PEG-PEI copolymer oral administration Notch inhibitors Medicine (General) R5-920 Desai D Prabhakar N Mamaeva V Şen Karaman D Lähdeniemi IAK Sahlgren C Rosenholm JM Toivola DM Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles
description	Diti Desai,1–4 Neeraj Prabhakar,2 Veronika Mamaeva,3,5 Didem Şen Karaman,2,4 Iris AK Lähdeniemi,1,6 Cecilia Sahlgren,3,7,* Jessica M Rosenholm,2,4,* Diana M Toivola1,6,* 1Cell Biology, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; 2Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; 3Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland; 4Laboratory of Physical Chemistry, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland; 5Department of Clinical Science, University of Bergen, Bergen, Norway; 6Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland; 7Department of Biomedical Engineering, Technical University of Eindhoven, Eindhoven, the Netherlands *These authors contributed equally to this work Abstract: 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. Keywords: intestinal targeting, PEG-PEI copolymer, Notch inhibition
format	article
author	Desai D Prabhakar N Mamaeva V Şen Karaman D Lähdeniemi IAK Sahlgren C Rosenholm JM Toivola DM
author_facet	Desai D Prabhakar N Mamaeva V Şen Karaman D Lähdeniemi IAK Sahlgren C Rosenholm JM Toivola DM
author_sort	Desai D
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_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_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_sort	targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently peg-pei functionalized mesoporous silica nanoparticles
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/92fc998002d34e38a964a3ec3b0d2a59
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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

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