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In vivo oral toxicological evaluation of mesoporous silica particles
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
Nanologica AB, Stockholm, och Dept of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University.
Nanologica AB, Stockholm, Sweden.
Nanologica AB, Stockholm, Sweden.
Vise andre og tillknytning
2013 (engelsk)Inngår i: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 8, nr 1, s. 57-64Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Mesoporous silica particles are highly promising nanomaterials for biomedical applications. They can be used to improve bioavailability, solubility and drug stability and to protect drugs from the acidic conditions of the stomach, leading to increased drug effectiveness. Their biocompatibility in vivo has recieved little attention, in particular regarding oral administration. Aim: To study the oral tolerance of micron-sized nanoporous folic acid-templated material-1 (cylindrical, 2D hexagonal pore structure) and nanometer-sized anionic-surfactant-templated mesoporous silica material-6 (cylindrical, 3D cubic pore structure) mesoporous silica particles in Sprague Dawley rats. Materials & methods: A dose stepwise procedure or range finding test was followed by a consequent confirmatory test. The confirmatory test included daily administrations of 2000 and 1200 mg/kg doses for nanoporous folic acid-templated material-1 and anionic-surfactant-templated mesoporous silica material-6, respectively. Results: The maximum tolerated dose for anionic-surfactant-templated mesoporous silica material-6 was not reached. Similar results were observed for nanometer-sized anionic-surfactant-templated mesoporous silica material-1 in most of the animals, although adverse effects were observed in some animals that are most probably due to the administration by oral gavage of the formulated particles. Conclusion: The results are promising for the use of mesoporous silica materials as drug-delivery systems in oral administration.

sted, utgiver, år, opplag, sider
2013. Vol. 8, nr 1, s. 57-64
HSV kategori
Forskningsprogram
Teknisk fysik med inriktning mot nanoteknologi och funktionella material
Identifikatorer
URN: urn:nbn:se:uu:diva-180100DOI: 10.2217/nnm.12.77ISI: 000314577800014PubMedID: 22891863OAI: oai:DiVA.org:uu-180100DiVA, id: diva2:548100
Tilgjengelig fra: 2012-08-29 Laget: 2012-08-29 Sist oppdatert: 2017-12-07bibliografisk 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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