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Large pore mesoporous silica induced weight loss in obese mice
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Nanologica AB, SE-11428 Stockholm, Sweden.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Diseases of the Developing World, GlaxoSmithKline, Madrid, Spanien.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
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2013 (English)In: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 9, no 9, 1353-1362 p.Article in journal (Refereed) Published
Abstract [en]

Background: There is a need for medical treatments to curb the rising rate of obesity. Weight reduction is correlated with a decrease in associated risk factors and cholesterol levels in humans. Amorphous silica particles have been found to exert a hypocholesterolemic effect in humans, making them popular dietary additives. Aim: To investigate the effect of mesoporous silica, which possess sharp pore size distributions, on: weight loss, cholesterol, triglycerides and glucose blood levels in obese mice. Materials & methods: Mesoporous silicas with differing pore size were mixed in the high-fat diet of obese mice. Results: Animals receiving large pore mesoporous silica with a high-fat diet show a significant reduction in body weight and fat composition, with no observable negative effects. Conclusion: Pore size is an important parameter for reduction of body weight and body fat composition by mesoporous silica, demonstrating promising signs for the treatment of obesity.

Place, publisher, year, edition, pages
2013. Vol. 9, no 9, 1353-1362 p.
Keyword [en]
body fat, body weight, cholesterol, high-fat diet, mesoporous silica, obesity
National Category
Other Medical Biotechnology Engineering and Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
URN: urn:nbn:se:uu:diva-195903DOI: 10.2217/nnm.13.138ISI: 000342071700012PubMedID: 24471500OAI: oai:DiVA.org:uu-195903DiVA: diva2:608640
Funder
Swedish Research Council, 2009-4716Novo NordiskSwedish Diabetes AssociationMagnus Bergvall FoundationCarl Tryggers foundation
Available from: 2013-02-28 Created: 2013-02-28 Last updated: 2017-07-05Bibliographically approved
In thesis
1. Toxicological and Immunomodulatory Properties of Mesoporous Silica Particles: Applications in Life Sciences
Open this publication in new window or tab >>Toxicological and Immunomodulatory Properties of Mesoporous Silica Particles: Applications in Life Sciences
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 76 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1023
Keyword
mesoporous silica, biocompatibility, adjuvants, drug delivery systems, obesity
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-195904 (URN)978-91-554-8605-1 (ISBN)
Public defence
2013-04-11, Polhemssalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 14:00 (English)
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Supervisors
Available from: 2013-03-21 Created: 2013-02-28 Last updated: 2013-05-02Bibliographically approved

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Kupferschmidt, NataliaGarcia-Bennett, Alfonso E.

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