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Particle transcytosis across intestinal epithelial cells exposed for Yersinia pseudotuberculosis: gene expression analysis and functional studies
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
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(English)Manuscript (Other academic)
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-93908OAI: oai:DiVA.org:uu-93908DiVA: diva2:167546
Available from: 2005-12-22 Created: 2005-12-22 Last updated: 2012-03-13
In thesis
1. Effects of Microparticulate Drug Delivery Systems: Tissue Responses and Transcellular Transport
Open this publication in new window or tab >>Effects of Microparticulate Drug Delivery Systems: Tissue Responses and Transcellular Transport
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Over the past decade, the development of macromolecular drugs based on peptides, proteins and nucleic acids has increased the interest in microparticulate drug delivery, i.e., the delivery of drug systems in the nanometer and micrometer ranges. However, little is known so far about the effect that microparticulate systems have on various tissues after administration. Additionally, the knowledge of mechanisms responsible for the uptake and transport of microparticles across the human intestine is incomplete and requires further investigation to improve both the safety profiles and the efficiency of these drug delivery systems.

This thesis is comprised of two parts. The first one investigates gene expression responses obtained from DNA arrays in local and distal tissues after microparticulate drug delivery. The second part focuses on the mechanisms responsible for the transport of microparticles across epithelial cells lining the intestine.

The results presented in the first part demonstrated that gene expression analysis offers a detailed picture of the tissue responses after intramuscular or pulmonary administration of microparticulate drug delivery systems compared to the traditional techniques used for such evaluations. In addition, DNA arrays provided a useful and sensitive tool for the initial characterization and evaluation of both local and distal tissue responses, making it possible to distinguish between gene expression patterns related to each studied delivery system.

The results presented in the second part demonstrated that the surface properties of the microparticle were important for the extent of transport across an in vitro model of the follicle-associated epithelium (FAE), comprised of intestinal epithelial cells specialized in particle transport (M cells). Another important finding was that the enteropathogen bacterium, Yersinia pseudotuberculosis, induced microparticle transport across the normal intestinal epithelium, represented by Caco-2 cells and excised human ileal tissue. This transport was most probably mediated by an increased capacity for macropinocytosis in the epithelial cells.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 59 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 25
Pharmaceutics, microparticles, vaccine, pDNA vaccine, cationic polymer, gene expression analysis (DNA array), Caco-2, follicle-associated epithelium (FAE), M cell, transcytosis, Yersinia pseudotuberculosis, Galenisk farmaci
National Category
Pharmaceutical Sciences
urn:nbn:se:uu:diva-6260 (URN)91-554-6433-5 (ISBN)
Public defence
2006-01-13, Room B21, BMC, Husargatan 3, Uppsala, 09:15
Available from: 2005-12-22 Created: 2005-12-22Bibliographically approved

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