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Mesoporous silica particles potentiate antigen specific T cell responses
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
(Experimental Asthma and Allergy Research, Centre for Allergy Research, The Institute of Environmental Medicine, KI, Stockholm, Sweden)
Dept of Medicine Solna, Translational Immunology Unit, KI, Stockholm, Sweden.
Vise andre og tillknytning
2014 (engelsk)Inngår i: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 9, nr 12, s. 1835-1846Artikkel i tidsskrift (Fagfellevurdert) Published
sted, utgiver, år, opplag, sider
2014. Vol. 9, nr 12, s. 1835-1846
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-195901DOI: 10.2217/nnm.13.170ISI: 000343904800006OAI: oai:DiVA.org:uu-195901DiVA, id: diva2:608636
Tilgjengelig fra: 2013-02-28 Laget: 2013-02-28 Sist oppdatert: 2017-12-06bibliografisk kontrollert
Inngår i avhandling
1. Toxicological and Immunomodulatory Properties of Mesoporous Silica Particles: Applications in Life Sciences
Åpne denne publikasjonen i ny fane eller vindu >>Toxicological and Immunomodulatory Properties of Mesoporous Silica Particles: Applications in Life Sciences
2013 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Mesoporous silica particles offer great potential benefits as vehicles for drug delivery and in other biomedical applications. They present a high loading capacity due their ordered and size-tuneable pores that allow molecules to be loaded and released. In addition, they offer the possibility to enhance oral bioavailability of drugs with limited aqueous solubility and to protect pH sensitive drugs from the acidic conditions in the stomach on their way to the intestine.

The aim of this thesis was to evaluate the biocompatibility and effects of mesoporous silica particles on immunocompetent cells. Subsequently, two potential life sciences applications were investigated: as adjuvants and as weight reduction agents.

Adjuvants are used in vaccines in order to enhance the immunological response towards attenuated and poorly immunogenic antigens. Their function can be mediated through dendritic cells which have a central role in the control of adaptive immunity including immunological memory. Our results show that different types of mesoporous silica particles were able to tune the development of T cells both in human cell cultures and in mice. In contrast to the approved adjuvant alum (aluminium salts) which is a specific inducer of Th2-type immune responses, the particles induced more Th1-like responses, which may be desired in vaccines against allergy and intracellular pathogens such as viruses. Particle exposure to macrophages did not affect their cell function which is crucial for tissue homeostasis, wound repair and in prevention of autoimmune responses. Likewise, the cytokine secretion was not affected, which suggest that macrophages would not modulate the immune response towards the particles.

Furthermore, mesoporous silica particles were highly tolerated at daily oral administrations of up to 2000 mg/kg doses for some of the materials prepared. Large pore mesoporous silica particles were shown to act as weight and body fat reduction agents without other observable pathological signs when administered in the diet of obese mice.

Together; those results are promising for the development of mesoporous silica as drug delivery systems and adjuvants for oral administration of drugs or vaccines. Additionally, large pore mesoporous silica materials are potential agents for the treatment of obesity.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2013. s. 76
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1023
Emneord
mesoporous silica, biocompatibility, adjuvants, drug delivery systems, obesity
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-195904 (URN)978-91-554-8605-1 (ISBN)
Disputas
2013-04-11, Polhemssalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 14:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2013-03-21 Laget: 2013-02-28 Sist oppdatert: 2013-05-02bibliografisk kontrollert

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