In Vitro and in vivo impact of silica nanoparticle design on biocompatibility

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Title In Vitro and in vivo impact of silica nanoparticle design on biocompatibility
Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Yu Tian
Date 2012-08
Description Silica nanoparticles (SiO2) have utility in a wide range of applications, such as biologic delivery platforms, imaging and diagnostic agents, and targeted therapeutic carriers. Recent improvements in regulating the geometry, porosity, and surface characteristics of SiO2 have further facilitated their biomedical applications. Concerns however remain about the toxic effects of SiO2 upon exposure to biological systems. The impacts of geometry, porosity, and surface characteristics of SiO2 on cellular toxicity and hemolytic activity were explored. It was shown that surface characteristics and porosity govern cellular toxicity. The cellular association of SiO2 increased in the following order: mesoporous SiO2 (aspect ratio 1, 2, 4, 8) < amine-modified mesoporous SiO2 (aspect ratio 1, 2, 4, 8) < amine-modified nonporous Stӧber SiO2 < nonporous Stӧber SiO2. Geometry did not seem to influence the extent of SiO2 cellular association. Hemolysis assay showed that the hemolytic activity was porosity- and geometry-dependent for pristine SiO2 and surface charge-dependent for amine-modified SiO2. The acute toxicity, biodistribution, and pharmacokinetics of SiO2 of systematically varied geometry, porosity, and surface characteristics were evaluated in immune-competent mice when administered intravenously. Results suggest that in vivo toxicity, biodistribution and pharmacokinetics of SiO2 were mainly influenced by nanoparticle porosity and surface characteristics. The maximum tolerated dose (MTD) increased in the following order: Mesoporous SiO2 (aspect ratio 1, 2, 8) at 30 - 65 mg/kg iv < amine-modified mesoporous SiO2 (aspect ratio 1, 2, 8) at 100 - 150 mg/kg < unmodified or amine-modified nonporous SiO2 at 450 mg/kg. The adverse reactions above MTDs were primarily caused by the mechanical obstruction of SiO2 in the vasculature that led to congestion in multiple vital organs and subsequent organ failure. The nanoparticles were taken up extensively by the liver and spleen. Mesoporous SiO2 exhibited higher accumulation in the lung than nonporous SiO2 of similar size. This accumulation was reduced by primary amine modification. Increasing the aspect ratio of amine-modified mesoporous SiO2 from 1 to 8 resulted in increased accumulation in the lung. These studies provide critical guidelines in rational design of SiO2 for nanomedicine applications.
Type Text
Publisher University of Utah
Subject MESH Nanoparticles; Silicon Dioxide; Biocompatible Materials; Drug Delivery Systems; Nanotubes, Carbon; Nanostructures; Nanotechnology; Particle Size; Toxicolog; Pharmacokinetics
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital reproduction of In Vitro and In Vivo Impact of Silica Nanoparticle Design on Biocompatibility. Spencer S. Eccles Health Sciences Library. Print version available at J. Willard Marriott Library Special Collections.
Rights Management Copyright © Tian Yu 2012
Format application/pdf
Format Medium application/pdf
Format Extent 10,087,730 bytes
Source Original in Marriott Library Special Collections, RS43.5 2012.Y8
ARK ark:/87278/s67w9mdw
Setname ir_etd
ID 196435
Reference URL https://collections.lib.utah.edu/ark:/87278/s67w9mdw
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