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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 275
Format	application/pdf
Setname	ir_etd
ID	1743139
OCR Text	Show 254 5.5 References [1] Q. He, Z. Zhang, F. Gao, Y. Li, J. Shi, In Vivo Biodistribution and Urinary Excretion of Mesoporous Silica Nanoparticles: Effects of Particle Size and PEGylation, Small, 7 (2011) 271-280. [2] M. Cho, W.-S. Cho, M. Choi, S.J. Kim, B.S. Han, S.H. Kim, H.O. Kim, Y.Y. Sheen, J. Jeong, The Impact of Size on Tissue Distribution and Elimination by Single Intravenous Injection of Silica Nanoparticles, Toxicology Letters, 189 (2009) 177-183. [3] L. Li, T. Liu, C. Fu, L. Tan, X. Meng, H. Liu, Biodistribution, Excretion, and Toxicity of Mesoporous Silica Nanoparticles After Oral Administration Depend on Their Shape, Nanomedicine; Nanotechnology, Biology and Medicine, 11 (2015) 1915-1924. [4] H. Yamada, C. Urata, Y. Aoyama, S. Osada, Y. Yamauchi, K. Kuroda, Preparation of Colloidal Mesoporous Silica Nanoparticles with Different Diameters and Their Unique Degradation Behavior in Static Aqueous Systems, Chemistry of Materials, 24 (2012) 14621471. [5] D. Shen, J. Yang, X. Li, L. Zhou, R. Zhang, W. Li, L. Chen, R. Wang, F. Zhang, D. Zhao, Biphase Stratification Approach to Three-Dimensional Dendritic Biodegradable Mesoporous Silica Nanospheres, Nano Letters, 14 (2014) 923-932. [6] V. Cauda, A. Schlossbauer, T. Bein, Biodegradation Study of Colloidal Mesoporous Silica Nanoparticles: Effect of Surface Functionalization with Organosilanes and Poly (ethylene glycol), Microporous and Mesoporous Materials, 132 (2010) 60-71. [7] D. Montero, C. Tachibana, J. Rahr Winther, C. Appenzeller-Herzog, Intracellular Glutathione Pools Are Heterogeneously Concentrated, Redox Biology, 1 (2013) 508-513. [8] M.L. Circu, T.Y. Aw, Glutathione and Modulation of Cell Apoptosis, Biochimica et Biophysica Acta, 1823 (2012) 1767-1777. [9] H.J. Forman, H. Zhang, A. Rinna, Glutathione: Overview of Its Protective Roles, Measurement, and Biosynthesis, Molecular Aspects of Medicine, 30 (2009) 1-12. [10] S.P. Hadipour Moghaddam, M. Yazdimamaghani, H. Ghandehari, GlutathioneSensitive Hollow Mesoporous Silica Nanoparticles For Controlled Drug Delivery, Journal of Controlled Release, 282 (2018) 62-75. [11] T. Yu, A. Malugin, H. Ghandehari, Impact of Silica Nanoparticle Design on Cellular Toxicity and Hemolytic Activity, ACS Nano, 5 (2011) 5717-5728. [12] J. Saikia, M. Yazdimamaghani, S.P. Hadipour Moghaddam, H. Ghandehari, interfaces, Differential Protein Adsorption and Cellular Uptake of Silica Nanoparticles Based on Size and Porosity, ACS Applied Materials and Interfaces, 8 (2016) 34820-34832. [13] S.P. Hadipour Moghaddam, J. Saikia, M. Yazdimamaghani, H. Ghandehari, interfaces, Redox-Responsive Polysulfide-Based Biodegradable Organosilica
Reference URL	https://collections.lib.utah.edu/ark:/87278/s6kc8x0s/1743139