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In vivo oral toxicological evaluation of mesoporous silica particles
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
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2013 (English)In: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 8, no 1, 57-64 p.Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
2013. Vol. 8, no 1, 57-64 p.
Keyword [en]
biovailability, mesoporous, oral administration, silica particle, toxicity
National Category
Other Environmental Biotechnology Microbiology Nano Technology
URN: urn:nbn:se:su:diva-88753DOI: 10.2217/NNM.12.77ISI: 000314577800014OAI: diva2:613082
Swedish Research CouncilEU, European Research Council, 261378


Available from: 2013-03-26 Created: 2013-03-26 Last updated: 2014-05-08Bibliographically approved
In thesis
1. Dissolving the Rocks: Solubility Enhancement of Active Pharmaceutical Ingredients using Mesoporous Silica
Open this publication in new window or tab >>Dissolving the Rocks: Solubility Enhancement of Active Pharmaceutical Ingredients using Mesoporous Silica
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Poor aqueous solubility is one of the greatest barriers for new drug candidates to enter toxicology studies, let alone clinical trials. This thesis focuses on contributing to solving this problem, evaluating the oral toxicity of mesoporous silica particles, and enhancing the apparent solubility and bioavailability of active pharmaceutical ingredients in vitro and in vivo using mesoporous silica particles.

Toxicological studies in rats showed that two types of mesoporous silica particles given by oral administration were well tolerated without showing clinical signs of toxicity. Solubility enhancement, including in vivo bioavailability and in vitro intracellular activity, has been evaluated for selected drug compounds. Mesoporous silica was shown to effectively increase drug solubility by stabilizing the amorphous state of APIs, such as itraconazole (anti-fungal), dasatinib (anti-cancer), atazanavir (anti-HIV) and PA-824 (anti-tuberculosis). Itraconazole was successfully loaded into a variety of porous silica materials showing a distinct improvement in the dissolution properties in comparison to non-porous silica materials (and the free drug). Microporosity in SBA-15 particles has advantages in stabilizing the supersaturation state of dasatinib. Small pore sizes show better confinement of atazanavir, contributing to a higher dissolution of the drug compound. In the in vivo animal studies, NFM-1 loaded with atazanavir shows a four-fold increase in bioavailability compared to free crystalline atazanavir. PA-824 has a higher dissolution rate and solubility after loading into AMS-6 mesoporous particles. The loaded particles show similar antibacterial activity as the free PA-824.

This thesis aims at highlighting some of the important factors enabling the selection of adequate mesoporous structures to enhance the pharmacokinetic profile of poorly water-soluble compounds, and preparing the scientific framework for uncovering the effects of drug confinement within mesopores of varying structural properties.

Place, publisher, year, edition, pages
Stockholm: Department of Materials and Environmental Chemistry (MMK), Stockholm University, 2014. 77 p.
mesoporous silica, drug delivery, solubility enhancement, active pharmaceutical ingredients, oral toxicity, confinement, crystallization, pharmaceutical excipients, bioavailability
National Category
Inorganic Chemistry
Research subject
Inorganic Chemistry
urn:nbn:se:su:diva-103190 (URN)978-91-7447-924-9 (ISBN)
Public defence
2014-06-18, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 13:00 (English)

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Submitted. Paper 3: Submitted. Paper 5: Submitted.

Available from: 2014-05-22 Created: 2014-05-08 Last updated: 2015-10-27Bibliographically approved

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