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Metabolic Toxicity Studies Using High Throughput Bioreactor Assay And Liquid Chromatography Coupled With Mass Spectrometry (Lc-Ms/ Ms), Dandan Li

Doctoral Dissertations

Metabolic toxicity is one of main concerns in drug discovery and development. High efficient and low cost metabolic toxicity assessment is still a major challenge for pharmaceutical industry. This thesis focuses on the development of high throughput in vitro metabolic toxicity assay coupling with liquid chromatography tandem mass spectrometry for metabolic adducts generation, characterization and quantitation. The key technology was based on electrostatic fabrication of polyelectrolytes and biomolecules on magnetic beads to form bioreactors in 96 well plate format and acquired metabolites induced toxicity molecular information by LC-MS experiments.

Chapter one will address the goals and significance of the metabolic …

Ultrasonication Assisted Layer-By-Layer Technology For The Preparation Of Multi-Functional Anticancer Drugs Paclitaxel And Lapatinib, Xingcai Zhang

Doctoral Dissertations

In this dissertation, ultrasonication assisted Layer-by-Layer (LbL) technology for the preparation of multifunctional poorly water-soluble anticancer drug nanoparticles, paclitaxel and lapatinib, has been developed. Many FDA approved drugs are very low soluble in water; therefore, it is very difficult to load and control their release and targeting efficiently, which greatly confines their application. The development of this method will pave the way for the development and application of those low soluble anticancer drugs.

In the first part of this dissertation, the first approach for powerful ultrasonication, the top-down approach (sonicating bulk drug crystals in polyelectrolyte solution), was successfully applied for …

Surface Morphology Of Platelet Adhesion Influenced By Activators, Inhibitors And Shear Stress, Melanie Groan Watson

Doctoral Dissertations

Platelet activation involves multiple events, one of which is the generation and release of nitric oxide (NO), a platelet aggregation inhibitor. Platelets simultaneously send and receive various agents that promote a positive and negative feedback control system during hemostasis. Although the purpose of platelet-derived NO is not fully understood, NO is known to inhibit platelet recruitment. NO's relatively large diffusion coefficient allows it to diffuse more rapidly than platelet agonists. It may thus be able to inhibit recruitment of platelets near the periphery of a growing thrombus before agonists have substantially accumulated in those regions.

Results from two studies in …

An Improved Layer-By-Layer Self-Assembly Technique To Generate Biointerfaces For Platelet Adhesion Studies: Dynamic Lbl, Juan Manuel Lopez

Doctoral Dissertations

Layer-by-layer self-assembly (LbL) is a technique that generates engineered nano-scale films, coatings, and particles. These nanoscale films have recently been used in multiple biomedical applications. Concurrently, microfabrication methods and advances in microfluidics are being developed and combined to create "Lab-on-a-Chip" technologies. The potential to perform complex biological assays in vitro as a first-line screening technique before moving on to animal models has made the concept of lab on a chip a valuable research tool.

Prior studies in the Biofluids Laboratory at Louisiana Tech have used layer-by-layer and in vitro biological assays to study thrombogenesis in a controlled, repeatable, engineered environment. …

Fabrication Of Bioactive Osteogenic Controlled-Release Systems, Cellular Platforms, And Cellular Capsules Using Layer -By -Layer Nanoassembly, Skylar Stewart-Clark

Doctoral Dissertations

There is an ever-increasing awareness that the field of tissue engineering offers many potential solutions to clinical problems. While advances along these lines have been made, the design and implementation of an "off the shelf" tissue is yet to be realized. Thus, the objectives of this work were largely aimed at the design and fabrication of biocompatible, bioactive structures which could be integrated into existing biomaterial products.

The electrostatic layer-by-layer (LbL) self-assembly technique was used to incorporate biologically relevant molecules within controlled release systems, cell culture platforms, and 3-D cellular capsules. Two delivery systems were investigated to determine the release …

Microparticulate Drug Reformulation Using Electrostatic Layer -By -Layer Assembly And Co-Entrapment With Anionic Phospholipids In Calcium Carbonate Matrix, Krishna Gopal

Doctoral Dissertations

Non-invasive drug delivery systems for therapeutic drugs are gaining prominence. One such system, the nasal delivery system, shows good prospect for effective delivery of some drugs, however, it is yet to be well established for others. The preparation of a reformulated drug and studying its in vitro characteristics is a crucial step in the process of adapting the new drug for nasal delivery systems. The purpose of this research is to study the effect of electrostatic layer by layer assembly of polyelectrolytes on PROMAXX®insulin microparticles and to study the chemical, physical and corresponding release properties of the resulting formulations. PROMAXX® …

Multicomponent Patterning Of Nanocomposite Polymer And Nanoparticle Films Using Photolithography And Layer-By-Layer Self -Assembly, Javeed Shaikh Mohammed

Doctoral Dissertations

In this dissertation, the fabrication, characterization, and application examples of 3D multicomponent nanocomposite micropatterns (MNMs) with precise spatial arrangements are described. The ability to produce such small-scale 3D structures with versatility in composition and structure is a new development based on the integration of nanoscale layer-by-layer (LbL) self-assembly and microscale photolithographic patterning, enabling construction of surfaces with microscale patterns that possess nanotopographies. The techniques used here are analogous to surface micromachining, except that the deposition materials are polymers, biological materials, and colloidal nanoparticles used to produce 3D MNMs. A key feature of the resulting 3D MNMs is that the physical …

Integration Of Micro Nano And Bio Technologies With Layer -By -Layer Self -Assembly, Dinesh Shankar Kommireddy

Doctoral Dissertations

In the past decade, layer-by-layer (LbL) nanoassembly has been used as a tool for immobilization and surface modification of materials with applications in biology and physical sciences. Often, in such applications, LbL assembly is integrated with various techniques to form functional surface coatings and immobilized matrices. In this work, integration of LbL with microfabrication and microfluidics, and tissue engineering are explored. In an effort to integrate microfabrication with LbL nanoassembly, microchannels were fabricated using soft-lithography and the surface of these channels was used for the immobilization of materials using LbL and laminar flow patterning. Synthesis of poly(dimethyldiallyl ammonium chloride)/poly(styrene sulfonate) …

Application Of Polyelectrolyte Layer-By-Layer Nano-Assembly For Surface Modification, Encapsulation And Controlled Release, Nikhil Anil Pargaonkar

Doctoral Dissertations

In this study, we applied the traditional Electrostatic layer-by-layer (ELBL) assembly procedure to fabricate nanothin films over flat surfaces, and modify particle surfaces to influence the drug particle size, and drug release. The ELBL assembly has previously been applied to fabricate multilayer nano-scale thin films, but its ability to instantaneously influencing particle size is unique. Other unique observations such as influence on drug release as a result of polymer complexation, and thermal changes occurring during layer fabrication are recorded.

The ELBL self-assembly process was applied to produce dexamethasone particles layered with various polyelectrolyte layer combinations. These combinations were further applied …

Novel Sensors For Neural Glucose Concentration Based On Enzyme Fluorescent Thin Films Fabricated On Nanoparticle Carriers Using Electrostatic Layer -By -Layer Assembly, Patrick Scott Grant

Doctoral Dissertations

Currently, there is no means by which rapidly fluctuating glucose and lactate levels can be monitored simultaneously. This dissertation demonstrates that by combining the broad-band versatility of fluorescence spectroscopy with nanoassembly methods, it is possible to construct micro- and nanoscale sensors with precise composition and short diffusion length constant. The work is significant because of its potential as a platform for discovery of basic normal physiological processes that have previously been hidden from researchers' views, more detailed studies of responses to drugs or other stimuli, and even clinical monitoring. The main goal of this work was to develop novel methods …

Patterning Layer -By -Layer Self -Assembled Multilayer By Lithography And Its Applications To Thin Film Devices, Feng Hua

Doctoral Dissertations

Nanoparticles are exciting materials because they exhibit unique electronic, catalytic, and optical properties. As a novel and promising nanobuilding block, it attracts considerable research efforts in its integration into a wide variety of thin film devices.

Nanoparticles were adsorbed onto the substrate with layer-by-layer self-assembly which becomes of great interest due to its suitability in colloid particle assembly. Without extremely high temperatures and sophisticated equipment, molecularly organized films in an exactly pre-designed order can grow on almost all the substrates in nature.

Two approaches generating spatially separated patterns comprised of nanoparticles are demonstrated, as well as two approaches patterning more …