Lee, Siu Fung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 89-91). / Abstracts in English and Chinese. / Content --- p.i / Acknowledgments --- p.iv / Abstract --- p.V / Abbreviations and Acronyms --- p.vii / Publications Originated from the Work of this Thesis --- p.ix / Chapter Chapter 1- --- Introduction / Chapter 1.1 --- Nanoparticle-based drug delivery --- p.1 / Chapter 1.2 --- Magnetic nanoparticle --- p.5 / Chapter 1.3 --- Iron oxide nanoparticle --- p.6 / Chapter 1.3.1 --- Coprecipitation --- p.7 / Chapter 1.3.2 --- Hydrothermal reaction --- p.7 / Chapter 1.3.3 --- Sol-gel reaction --- p.8 / Chapter 1.3.4 --- Solvothermal reaction --- p.8 / Chapter 1.3.5 --- Architecture of iron oxide nanoparticles as drug carriers --- p.9 / Chapter 1.4 --- Supramolecular chemistry involved in controlled release drug delivery system --- p.10 / Chapter 1.5 --- Nano valve --- p.15 / Chapter 1.6 --- Aim of project --- p.17 / Chapter Chapter 2- --- Stimuli-Responsive Drug Delivery Nanosystems based on Fe3O4@SiO2@crown ether Nanoparticles / Chapter 2.1 --- Background --- p.19 / Chapter 2.2 --- Synthesis of the dibenzo-crown ethers --- p.21 / Chapter 2.3 --- Synthetic method of functionalized nanoparticles --- p.22 / Chapter 2.4 --- Characterization of dibenzo-crown ethers --- p.25 / Chapter 2.4.1 --- Nuclear magnetic resonance (NMR) spectroscopy --- p.25 / Chapter 2.4.2 --- Mass spectrometry (MS) --- p.27 / Chapter 2.4.3 --- Infrared (IR) spectroscopy --- p.28 / Chapter 2.5 --- Characterization of nanoparticles --- p.29 / Chapter 2.5.1 --- Transmission electron microscopy (TEM) --- p.29 / Chapter 2.5.2 --- Energy-dispersive X-ray (EDX) spectroscopy --- p.34 / Chapter 2.5.3 --- IR spectroscopy --- p.39 / Chapter 2.5.4 --- Thermogravimetric analysis (TGA) --- p.41 / Chapter 2.5.5 --- Nitrogen absorption/desorption isotherms --- p.44 / Chapter 2.6 --- Biological study of functionalized nanoparticles --- p.45 / Chapter 2.6.1 --- Cytotoxicity study --- p.45 / Chapter 2.6.2 --- Cell adhesion study --- p.46 / Chapter 2.6.3 --- Cell proliferation study --- p.47 / Chapter 2.6.4 --- Cellular uptake of nanoparticles --- p.50 / Chapter 2.7 --- Drug loading under different stimuli --- p.54 / Chapter 2.8 --- Drug release profile of nanoparticles --- p.61 / Chapter 2.9 --- MRI study of nanoparticles --- p.67 / Chapter 2.10 --- Conclusion --- p.69 / Chapter Chapter 3- --- Experimental Procedures / Chapter 3.1 --- General Information --- p.72 / Chapter 3.2 --- General procedure of synthesis of polyethers 3a-b --- p.73 / Chapter 3.2.1 --- Synthesis of 3a --- p.74 / Chapter 3.2.2 --- Synthesis of 3b --- p.74 / Chapter 3.3 --- General procedure of synthesis of diesters 4a-b --- p.75 / Chapter 3.3.1 --- Synthesis of 4a --- p.75 / Chapter 3.3.2 --- Synthesis of 4b --- p.76 / Chapter 3.4 --- General procedure of synthesis of dibenzo crown ether esters 5a-c --- p.77 / Chapter 3.4.1 --- Synthesis of 5a --- p.77 / Chapter 3.4.2 --- Synthesis of 5b --- p.78 / Chapter 3.4.3 --- Synthesis of 5c --- p.78 / Chapter 3.5 --- General procedure of synthesis of dibenzo-crown ethers la-c --- p.79 / Chapter 3.5.1 --- Synthesis of la --- p.80 / Chapter 3.5.2 --- Synthesis of lb --- p.80 / Chapter 3.5.3 --- Synthesis of lc --- p.81 / Chapter 3.6 --- Preparation of superparamagnetic Fe3O4 nanoparticle with an average diameter 120 nm --- p.81 / Chapter 3.7 --- Preparation of core/shell Fe3O4@SiO2 nanoparticle --- p.82 / Chapter 3.8 --- Preparation of Fe3O4@SiO2@meso(CTAB)-Si02 nanoparticle --- p.82 / Chapter 3.9 --- Preparation of Fe3O4@SiO2@meso(CTAB)-SiO2-NH2 nanoparticle --- p.83 / Chapter 3.10 --- Preparation of Fe3O4@SiO2@meso-SiO2@crown ether(a-c) nanoparticles --- p.83 / Chapter 3.11 --- Protocol of biological study of functionalized nanoparticles --- p.84 / Chapter 3.11.1 --- MTT protocol --- p.84 / Chapter 3.11.2 --- Cytotoxicity study --- p.84 / Chapter 3.11.3 --- Cell adhesion study --- p.85 / Chapter 3.11.4 --- Cell proliferation study --- p.85 / Chapter 3.11.5 --- Cellular uptake of functionalized nanoparticles --- p.85 / Chapter 3.12 --- Drug loading of functionalized nanoparticles --- p.86 / Chapter 3.13 --- Drug release profile of functionalized nanoparticles --- p.87 / Chapter 3.14 --- MRI study of nanoparticles --- p.87 / References --- p.89 / Appendix / List of Spectra --- p.A-1

Introduction: Embolic agents are used to block blood flow of hypervascular tumours, ultimately resulting in target tissue necrosis. However, this therapy is limited by the formation of new blood vessels within the tumour, a process known as angiogenesis. Targeting angiogenesis led to the discovery of anti-angiogenic factors, large molecular weight proteins that can block the angiogenic process. The aim of this research is development of poly (vinyl alcohol) (PVA) aqueous solutions that cross-link in situ to form a hydrogel that functions as an embolic agent for delivery of macromolecular drugs. Methods: PVA (14 kDa, 83% hydrolysed), functionalised by 7 acrylamide groups per chain, was used to prepare 10, 15, and 20wt% non-degradable hydrogels, cured by UV or redox initiation. Structural properties were characterised and the release of FITCDextran (20kDa) was quantified. Degradable networks were then prepared by attaching to PVA (83% and 98 % hydrolysed) ester linkages with an acrylate end group. The effect on degradation profiles was assessed by varying parameters such as macromer concentration, cross-linking density, polymer backbone and curing method. To further enhance the technology, radiopaque degradable PVA was synthesised, and degradation profiles were determined. Cell growth inhibition of modified PVA and degradable products were also investigated. Results: Redox initiation resulted in non-degradable PVA networks of well-controlled structural properties. Increasing the solid content from 10 to 20wt% prolonged the release time from few hours to ~ 2 days but had no effect on the percent release, with only a maximum release of 65% achieved. Ester attachment to the PVA allowed flexibility in designing networks of variable swelling behaviors and degradation times allowing ease of tailoring for specific clinical requirements. Synthesis of radiopaque degradable PVA hydrogels was successful without affecting the polymer solubility in water or its ability to polymerize by redox. This suggested that this novel hydrogel is a potential liquid embolic with enhanced X-ray visibility. Degradable products had negligible cytotoxicity. Conclusion: Novel non-degradable and radiopaque degradable PVA hydrogels cured by redox initiation were developed in this research. The developed PVA hydrogels showed characteristics in vitro that are desirable for the in vivo application as release systems for anti-angiogenic factors.

No description available.

Thesis (Ph. D.)--West Virginia University, 2004. / Title from document title page. Document formatted into pages; contains xviii, 279 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.

Introduction: Embolic agents are used to block blood flow of hypervascular tumours, ultimately resulting in target tissue necrosis. However, this therapy is limited by the formation of new blood vessels within the tumour, a process known as angiogenesis. Targeting angiogenesis led to the discovery of anti-angiogenic factors, large molecular weight proteins that can block the angiogenic process. The aim of this research is development of poly (vinyl alcohol) (PVA) aqueous solutions that cross-link in situ to form a hydrogel that functions as an embolic agent for delivery of macromolecular drugs. Methods: PVA (14 kDa, 83% hydrolysed), functionalised by 7 acrylamide groups per chain, was used to prepare 10, 15, and 20wt% non-degradable hydrogels, cured by UV or redox initiation. Structural properties were characterised and the release of FITCDextran (20kDa) was quantified. Degradable networks were then prepared by attaching to PVA (83% and 98 % hydrolysed) ester linkages with an acrylate end group. The effect on degradation profiles was assessed by varying parameters such as macromer concentration, cross-linking density, polymer backbone and curing method. To further enhance the technology, radiopaque degradable PVA was synthesised, and degradation profiles were determined. Cell growth inhibition of modified PVA and degradable products were also investigated. Results: Redox initiation resulted in non-degradable PVA networks of well-controlled structural properties. Increasing the solid content from 10 to 20wt% prolonged the release time from few hours to ~ 2 days but had no effect on the percent release, with only a maximum release of 65% achieved. Ester attachment to the PVA allowed flexibility in designing networks of variable swelling behaviors and degradation times allowing ease of tailoring for specific clinical requirements. Synthesis of radiopaque degradable PVA hydrogels was successful without affecting the polymer solubility in water or its ability to polymerize by redox. This suggested that this novel hydrogel is a potential liquid embolic with enhanced X-ray visibility. Degradable products had negligible cytotoxicity. Conclusion: Novel non-degradable and radiopaque degradable PVA hydrogels cured by redox initiation were developed in this research. The developed PVA hydrogels showed characteristics in vitro that are desirable for the in vivo application as release systems for anti-angiogenic factors.

Introduction: Embolic agents are used to block blood flow of hypervascular tumours, ultimately resulting in target tissue necrosis. However, this therapy is limited by the formation of new blood vessels within the tumour, a process known as angiogenesis. Targeting angiogenesis led to the discovery of anti-angiogenic factors, large molecular weight proteins that can block the angiogenic process. The aim of this research is development of poly (vinyl alcohol) (PVA) aqueous solutions that cross-link in situ to form a hydrogel that functions as an embolic agent for delivery of macromolecular drugs. Methods: PVA (14 kDa, 83% hydrolysed), functionalised by 7 acrylamide groups per chain, was used to prepare 10, 15, and 20wt% non-degradable hydrogels, cured by UV or redox initiation. Structural properties were characterised and the release of FITCDextran (20kDa) was quantified. Degradable networks were then prepared by attaching to PVA (83% and 98 % hydrolysed) ester linkages with an acrylate end group. The effect on degradation profiles was assessed by varying parameters such as macromer concentration, cross-linking density, polymer backbone and curing method. To further enhance the technology, radiopaque degradable PVA was synthesised, and degradation profiles were determined. Cell growth inhibition of modified PVA and degradable products were also investigated. Results: Redox initiation resulted in non-degradable PVA networks of well-controlled structural properties. Increasing the solid content from 10 to 20wt% prolonged the release time from few hours to ~ 2 days but had no effect on the percent release, with only a maximum release of 65% achieved. Ester attachment to the PVA allowed flexibility in designing networks of variable swelling behaviors and degradation times allowing ease of tailoring for specific clinical requirements. Synthesis of radiopaque degradable PVA hydrogels was successful without affecting the polymer solubility in water or its ability to polymerize by redox. This suggested that this novel hydrogel is a potential liquid embolic with enhanced X-ray visibility. Degradable products had negligible cytotoxicity. Conclusion: Novel non-degradable and radiopaque degradable PVA hydrogels cured by redox initiation were developed in this research. The developed PVA hydrogels showed characteristics in vitro that are desirable for the in vivo application as release systems for anti-angiogenic factors.

Thesis (Ph. D.)--Lund University.

Thesis (Ph. D.)--Lund University.

Thesis (Ph.D)--Biomedical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Murthy, Niren; Committee Member: Bellamkonda, Ravi; Committee Member: Davis, Michael; Committee Member: May, Sheldon; Committee Member: Milam, Valeria. Part of the SMARTech Electronic Thesis and Dissertation Collection.

No description available.