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TNF-α, TGF-β, and LTα1/β2 induces particle uptake and augments B-cell-induced particle transcytosis in intestinal epithelial cells
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-92590OAI: oai:DiVA.org:uu-92590DiVA: diva2:165731
Available from: 2005-02-07 Created: 2005-02-07 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Particle Transcytosis Across the Human Intestinal Epithelium: Model Development and Target Identification for Improved Drug Delivery
Open this publication in new window or tab >>Particle Transcytosis Across the Human Intestinal Epithelium: Model Development and Target Identification for Improved Drug Delivery
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The use of nano- and micro-particulate carriers as delivery systems for oral vaccines has been under investigation for several decades. Surprisingly little is known of their uptake in the human intestine, despite the fact that substantial improvement is required to achieve adequate immune responses in man after oral administration.

In this thesis, various aspects of particle transcytosis across the human intestinal epithelium were studied, in order to identify strategies for improved uptake of nano- and micro-particulate drug delivery systems.

The follicle associated epithelium (FAE) overlying Peyer´s patches contains M-cells, which have an increased capacity for uptake of particulate antigens. Therefore, a model of human FAE was developed to study mechanisms of particle uptake and transport.

Receptors that could be used for targeting to the FAE had previously not been identified in humans. By use of the model FAE, two new targets were identified on human intestinal FAE; CD9 and β1-integrin. Furthermore, studies of isolated human intestinal tissue showed that an integrin-adherent peptide motif, RGD, could be utilized to achieve selective and improved transport of nanoparticles into human Peyer´s patches.

Studies of factors influencing intestinal particle uptake and transcytosis revealed that two cytokines, TNF-α and LTα1/β2, but also one growth factor, TGF-β1, induced uptake of particles in Caco-2 cells and transcytosis of particles in the model FAE. Furthermore, it was shown that an enteric bacterium, Yersinia Pseudotuberculosis, could trigger uptake and transcytosis of particles across model absorptive epithelial cells.

In conclusion, this thesis provides a platform for further investigations of particle transcytosis across the human intestinal epithelium. The identification of two new proteins with increased expression in human FAE and a targeting sequence that improves particle uptake into Peyer’s patches, gives new hope for the development of subunit oral vaccines.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 62 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 3
Pharmaceutics, M-cell, FAE, Peyer´s patches, oral vaccination, uptake, endocytosis, Galenisk farmaci
National Category
Pharmaceutical Sciences
urn:nbn:se:uu:diva-4780 (URN)91-554-6145-X (ISBN)
Public defence
2005-03-04, Room B41, Uppsala Biomedical Centre, Husargatan 5, Uppsala, 10:15
Available from: 2005-02-07 Created: 2005-02-07Bibliographically approved

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