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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 137
Format	application/pdf
Setname	ir_etd
ID	1743001
OCR Text	Show 116 [24] V.I. Lushchak, Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions, Journal of Amino Acids, 16 (2012) 26-31. [25] G. Wu, Y.-Z. Fang, S. Yang, J.R. Lupton, N.D. Turner, Glutathione Metabolism and Its Implications For Health, The Journal of Nutrition, 134 (2004) 489-492. [26] E.S. Arner, A. Holmgren, Physiological Functions of Thioredoxin and Thioredoxin Reductase, European Journal of Biochemistry, 267 (2000) 6102-6109. [27] A.P. Senft, T.P. Dalton, H.G. Shertzer, Determining Glutathione and Glutathione Disulfide Using the Fluorescence Probe O-phthalaldehyde, Analytical Biochemistry, 280 (2000) 80-86. [28] H.L. Herd, A. Malugin, H. Ghandehari, Silica Nanoconstruct Cellular Toleration Threshold In Vitro, Journal of Controlled Release, 153 (2011) 40-48. [29] H.H. Gustafson, D. Holt-Casper, D.W. Grainger, H. Ghandehari, Nanoparticle Uptake: The Phagocyte Problem, Nano Today, 10 (2015) 487-510. [30] Slowing, II, C.W. Wu, J.L. Vivero-Escoto, V.S. Lin, Mesoporous Silica Nanoparticles for Reducing Hemolytic Activity Towards Mammalian Red Blood Cells, Small, 5 (2009) 57-62. [31] L. Sun, Y. Li, X. Liu, M. Jin, L. Zhang, Z. Du, C. Guo, P. Huang, Z. Sun, Cytotoxicity and Mitochondrial Damage Caused by Silica Nanoparticles, Toxicolology In Vitro, 25 (2011) 1619-1629. [32] Y. Park, H. Bae, Y. Jang, S. Jeong, H. Lee, W. Ryu, M. Yoo, Y. Kim, M. Kim, J. Lee, J. Jeong, S. Son, Effect of the Size and Surface Charge of Silica Nanoparticles on Cutaneous Toxicity, Molecular and Cellular Toxicology, 9 (2013) 67-74. [33] H. Maeda, J. Wu, T. Sawa, Y. Matsumura, K. Hori, Tumor Vascular Permeability and the EPR Effect in Macromolecular Therapeutics: A Review, Journal of Controlled Release, 65 (2000) 271-284. [34] U.T. Phan, B. Arunachalam, P. Cresswell, Gamma-Interferon-Inducible Lysosomal Thiol Reductase (GILT). Maturation, Activity, and Mechanism of Action, The Journal of Biological Chemistry, 275 (2000) 25907-25914. [35] D.S. Collins, E.R. Unanue, C.V. Harding, Reduction of Disulfide Bonds Within Lysosomes is a Key Step in Antigen Processing, The Journal of Immunology, 147 (1991) 4054-4059. [36] T. Berg, T. Gjøen, O. Bakke, Physiological Functions of Endosomal Proteolysis, Biochemical Journal, 307 (1995) 313-326. [37] B. Arunachalam, U.T. Phan, H.J. Geuze, P. Cresswell, Enzymatic Reduction of Disulfide Bonds in Lysosomes: Characterization of a Gamma-Interferon-Inducible
Reference URL	https://collections.lib.utah.edu/ark:/87278/s6kc8x0s/1743001