In Vitro Intestinal Uptake And Permeability Of Fluorescently-Labelled Hyaluronic Acid Nanogels

Miguel Xavier,1 Lorena García-Hevia,1 Isabel R Amado,1,2 Lorenzo Pastrana,1 Catarina Gonçalves1 1Department of Life Sciences, International Iberian Nanotechnology Laboratory, Braga 4715-330, Portugal; 2Department of Food and Analytical Chemistry, Faculty of Sciences, University...

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Autores principales:	Xavier M, García-Hevia L, Amado IR, Pastrana L, Gonçalves C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	oral delivery in vitro models nanogels intestinal permeability cellular uptake Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9374eca33da34c689a55f0b640cb67c1
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spelling	oai:doaj.org-article:9374eca33da34c689a55f0b640cb67c12021-12-02T07:53:09ZIn Vitro Intestinal Uptake And Permeability Of Fluorescently-Labelled Hyaluronic Acid Nanogels1178-2013https://doaj.org/article/9374eca33da34c689a55f0b640cb67c12019-11-01T00:00:00Zhttps://www.dovepress.com/in-vitro-intestinal-uptake-and-permeability-of-fluorescently-labelled--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Miguel Xavier,1 Lorena García-Hevia,1 Isabel R Amado,1,2 Lorenzo Pastrana,1 Catarina Gonçalves1 1Department of Life Sciences, International Iberian Nanotechnology Laboratory, Braga 4715-330, Portugal; 2Department of Food and Analytical Chemistry, Faculty of Sciences, University of Vigo, Ourense 32004, SpainCorrespondence: Catarina GonçalvesDepartment of Life Sciences, International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, Braga 4715-330, PortugalEmail catarina.goncalves@inl.intBackground: Oral administration remains the most common mode of drug delivery. However, orally administered bioactive compounds must first survive digestion and then be absorbed at the intestine in order to reach other tissues or organs. The efficiency of both processes can be improved by encapsulation or conjugation with polymeric nanoparticles. Here we report the synthesis of amphiphilic hyaluronic acid (HyA) nanogels as nanocarriers for drug delivery.Methods: HyA nanogels were prepared by self-assembly from amphiphilic HyA conjugates produced by grafting hydrophobic alkyl chains to the HyA backbone. The dye Cy5.5 was covalently bonded and used for tracking. The nanogels were characterised according to their structure, size and zeta potential, as well as biocompatibility towards an intestinal epithelial cell line. The uptake and intestinal permeability of the nanogels were assessed using in vitro models, which physiological relevance was verified regarding the morphology of the epithelium, the production of mucus, the expression of occludin and the transepithelial electrical resistance.Results: The covalent binding of Cy5.5 did not affect significantly the size and surface charge of the nanogels at 125.1 ± 3.2 nm and −57.6 ± 6.2 mV respectively after labelling. Studies of biocompatibility showed that the nanogels were non-toxic to Caco-2 cells up to the concentration of 0.1 mg∙mL−1. The presence of mucus affected the nanogel uptake and highlighted the importance of considering mucus-producing cells in in vitro intestinal models. The uptake or adsorption to a Caco-2/HT29-MTX co-culture (8.1%) was higher than with single Caco-2 cell cultures (4.3%). Interestingly, both models led to minute (<0.5%) permeation of the nanogels across the intestinal barrier.Conclusion: The HyA nanogels demonstrated to be mucoadhesive and effectively uptaken by intestinal cells. Both are determinant features for sustained release, but if systemic delivery is envisaged further modification with targeting moieties could be important to improve the nanogel permeability.Keywords: oral delivery, in vitro models, nanogels, intestinal permeability, cellular uptakeXavier MGarcía-Hevia LAmado IRPastrana LGonçalves CDove Medical Pressarticleoral deliveryin vitro modelsnanogelsintestinal permeabilitycellular uptakeMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 9077-9088 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	oral delivery in vitro models nanogels intestinal permeability cellular uptake Medicine (General) R5-920
spellingShingle	oral delivery in vitro models nanogels intestinal permeability cellular uptake Medicine (General) R5-920 Xavier M García-Hevia L Amado IR Pastrana L Gonçalves C In Vitro Intestinal Uptake And Permeability Of Fluorescently-Labelled Hyaluronic Acid Nanogels
description	Miguel Xavier,1 Lorena García-Hevia,1 Isabel R Amado,1,2 Lorenzo Pastrana,1 Catarina Gonçalves1 1Department of Life Sciences, International Iberian Nanotechnology Laboratory, Braga 4715-330, Portugal; 2Department of Food and Analytical Chemistry, Faculty of Sciences, University of Vigo, Ourense 32004, SpainCorrespondence: Catarina GonçalvesDepartment of Life Sciences, International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, Braga 4715-330, PortugalEmail catarina.goncalves@inl.intBackground: Oral administration remains the most common mode of drug delivery. However, orally administered bioactive compounds must first survive digestion and then be absorbed at the intestine in order to reach other tissues or organs. The efficiency of both processes can be improved by encapsulation or conjugation with polymeric nanoparticles. Here we report the synthesis of amphiphilic hyaluronic acid (HyA) nanogels as nanocarriers for drug delivery.Methods: HyA nanogels were prepared by self-assembly from amphiphilic HyA conjugates produced by grafting hydrophobic alkyl chains to the HyA backbone. The dye Cy5.5 was covalently bonded and used for tracking. The nanogels were characterised according to their structure, size and zeta potential, as well as biocompatibility towards an intestinal epithelial cell line. The uptake and intestinal permeability of the nanogels were assessed using in vitro models, which physiological relevance was verified regarding the morphology of the epithelium, the production of mucus, the expression of occludin and the transepithelial electrical resistance.Results: The covalent binding of Cy5.5 did not affect significantly the size and surface charge of the nanogels at 125.1 ± 3.2 nm and −57.6 ± 6.2 mV respectively after labelling. Studies of biocompatibility showed that the nanogels were non-toxic to Caco-2 cells up to the concentration of 0.1 mg∙mL−1. The presence of mucus affected the nanogel uptake and highlighted the importance of considering mucus-producing cells in in vitro intestinal models. The uptake or adsorption to a Caco-2/HT29-MTX co-culture (8.1%) was higher than with single Caco-2 cell cultures (4.3%). Interestingly, both models led to minute (<0.5%) permeation of the nanogels across the intestinal barrier.Conclusion: The HyA nanogels demonstrated to be mucoadhesive and effectively uptaken by intestinal cells. Both are determinant features for sustained release, but if systemic delivery is envisaged further modification with targeting moieties could be important to improve the nanogel permeability.Keywords: oral delivery, in vitro models, nanogels, intestinal permeability, cellular uptake
format	article
author	Xavier M García-Hevia L Amado IR Pastrana L Gonçalves C
author_facet	Xavier M García-Hevia L Amado IR Pastrana L Gonçalves C
author_sort	Xavier M
title	In Vitro Intestinal Uptake And Permeability Of Fluorescently-Labelled Hyaluronic Acid Nanogels
title_short	In Vitro Intestinal Uptake And Permeability Of Fluorescently-Labelled Hyaluronic Acid Nanogels
title_full	In Vitro Intestinal Uptake And Permeability Of Fluorescently-Labelled Hyaluronic Acid Nanogels
title_fullStr	In Vitro Intestinal Uptake And Permeability Of Fluorescently-Labelled Hyaluronic Acid Nanogels
title_full_unstemmed	In Vitro Intestinal Uptake And Permeability Of Fluorescently-Labelled Hyaluronic Acid Nanogels
title_sort	in vitro intestinal uptake and permeability of fluorescently-labelled hyaluronic acid nanogels
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/9374eca33da34c689a55f0b640cb67c1
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In Vitro Intestinal Uptake And Permeability Of Fluorescently-Labelled Hyaluronic Acid Nanogels

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