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Title Polysulfide-based biodegradable silica nanoparticles: synthesis, characterization, and biological fate
Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Moghaddam, Seyyed Pouya Hadipour
Date 2019
Description Silica nanoparticles (SiO2 NPs) have attracted attention for delivery of bioactive and imaging agents due to their stability, robustness, ease of synthesis and scale up and the ability to protect active pharmaceutical ingredients. For these constructs to advance to clinical use detailed understanding of the influence of physicochemical properties on degradation and biological fate is needed. Majority of SiO2 NPs studied to-date lack controlled biodegradability under physiologic conditions. Another drawback is associated with low loading capacity and the limited control over release from porous nanostructures. Despite significant research, there is a lack of comparative and systematic in vitro and in vivo investigation of SiO2 NPs degradation profiles. In this dissertation, glutathione (GSH)-sensitive polysulfide-based biodegradable SiO2 NPs with variations in size, porosity, and composition were synthesized and characterized. Their degradation was evaluated. Results indicate that nonporous nanoparticles undergo surface erosion while porous nanoparticles undergo both surface and bulk erosion under reducing environment. Tunable GSH-sensitive hollow mesoporous SiO2 NPs were developed using a compositional and structural difference-based selective etching strategy. These hollow nanoparticles contained disulfide (S-S) linkages in the outer shell which were reduced by GSH. The particles showed a high loading capacity for doxorubicin as a model drug. A series of particles with variations in size, porosity, density, and composition were compared iv for their degradation in vitro and in CD-1 mice. Results of these studies indicate that nanoparticle porosity and composition as well as the pH of the medium play the predominant roles for the degradation of SiO2 NPs. These studies have provided a baseline for designing biodegradable silica nanoparticles for specific drug delivery applications.
Type Text
Publisher University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Rights Management © Seyyed Pouya Hadipour Moghaddam
Format application/pdf
Format Medium application/pdf
ARK ark:/87278/s6kc8x0s
Setname ir_etd
ID 1742864
Reference URL https://collections.lib.utah.edu/ark:/87278/s6kc8x0s

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Title Page 276
Format application/pdf
Setname ir_etd
ID 1743140
OCR Text Show
Reference URL https://collections.lib.utah.edu/ark:/87278/s6kc8x0s/1743140