MSc (Med), Faculty of Health Sciences, University of the Witwatersrand, 2010 / The poor bioavailability of drugs has been identified as the single most important challenge in oral drug delivery. Prominent among the factors responsible for this are the metabolic activity of the intestinal and hepatic cytochrome P450 enzyme family. This dissertation presents novel cytochrome P450 inhibitors generated through the application of computational modeling of known cytochrome P450-substrate and cytochrome P450-inhibitor interactions. In vitro metabolism of felodipine by cytochrome P450 3A4-expressed human liver microsomes was optimized yielding a typical Michaelis-Menten plot through the application of Enzyme Kinetic Module software from where the enzyme kinetic parameters were determined. Quercetin, naringin and naringenin which are the major phytochemical component of grapefruit juice, a well known cytochrome P450 3A4 inhibitor, were separately incubated in human liver microsomes together with felodipine at concentration equivalent to the determined Michaelis-Menten Constant (Km) value. Compared to verapamil, a known competitive inhibitor of cytochrome P450 3A4, all three flavonoids inhibited felodipine metabolism with IC50 values of 208.65, 177.81 and 121.97μM respectively confirming earlier suggestions that the flavonoid contents of grapefruit juice are responsible for known grapefruit-drug interactions. Following a detailed study of the quantitative structure-activity relationship of these flavonoids and verapamil, their binding properties with cytochrome P3A4, the amino acid sequence and binding affinity of cytochrome P3A4, computational modeling software on a non-silicon graphic system was employed to generate pharmaceutical grade and commercially available polymers based on activity prediction aided by computational biomimetism and simulations. Thus grapefruit-felodipine interaction (a typical cytochrome P3A4 inhibitor-substrate interaction) served as the basis for the computational modeling where several modeled compounds including 8-arm-poly(ethylene glycol), o-(2-aminoethyl)-o-methyl poly(ethylene glycol), 4-arm-poly(ethylene glycol) (MW=10000g/mol and 20000g/mol) and poly (L-lysine) were generated and investigated for inhibitory activity against felodipine metabolism by human liver microsomes and human intestinal microsomes where 8-arm-poly(ethylene glycol) demonstrated the highest inhibitory potency with an IC50 value of 7.22μM. An ex vivo method employing freshly excised pig intestinal tissue was developed and validated to investigate the inhibition of cytochrome P450-induced drug metabolism in living tissues. Both naringenin and 8-arm-poly(ethylene glycol) exhibited significant inhibitory effects against felodipine metabolism in pig intestinal tissues. The ex vivo studies yielding IC50 values of 179.88 and 487.75μM for naringenin and 8-arm-poly(ethylene glycol) respectively demonstrated a promising in vivo inhibitory activity against intestinal cytochrome P450 3A4. The potential utility of 8-arm-poly(ethylene glycol) in oral drug delivery was investigated by assessing its influence on the formulation and behavior of tablet matrices. Results showed that 8-arm-poly(ethylene glycol) possessed satisfactory compressional, binding and friability characteristics with acceptable drug release profiles. In vivo studies of the effects of 8-arm-poly(ethylene glycol) on the oral bioavailability of felodipine were performed on the Large White pig model. Compared to controls, a >100% increase in plasma felodipine levels was observed. The outcome of this research presents 8-arm-poly(ethelyne glycol) as a promising oral bioavailability enhancer.

Thesis (Ph. D.)--University of Missouri-Columbia, 2006. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (July 18, 2008) Includes bibliographical references.

As the Worlds energy demand is increasing we need more of our energy to be generated from resources that affect the climate as little as possible. Solar power could be the solution if there were solar panels with a less energy demanding production than the established silicon based solar modules. Printable organic solar cells will enable a cheap production process, thus they are mainly made out of polymers in solution. However, to be able to decrease the total cost of the solar modules the commonly used indium tin oxide (ITO) for the transparent electrode needs to be replaced by a less expensive material. If the cheap, high conductive and transparent polymer poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) could replace ITO the cost of organic solar modules would significantly decrease. For PEDOT:PSS to be able to replace ITO there are requirements that have to be met. The transparent electrode needs to be apart from transparent, highly conductive, have a low contact resistance to the other materials in the organic solar cell and be printable. In this study it has been shown that the PEDOT:PSS film with Zonyl and Diethylene Glycol (DEG) as an secondary dopant, is capable of laminating to thin films made out of PEDOT:PSS, metal or a polymer fullerene blend. The contact resistances between two PEDOT:PSS films and PEDOT:PSS film and a metal film proved to be low. When laminating to a metal film an interlayer of Silver Nano Wires (AgNW) was needed to achieve a low contact resistance.

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No description available.

The aim of this research was to study the influence of altered water availability on stomatal patterns of leaves. A baseline study of leaves stomatal indices, (stomatal as a proportional of all epidermal cells) stomatal density, (number of stomatal per unit area of epidermis) epidermal cell density, epidermal cell length and stomatal length and width was made in wheat, and sorghum cultivars; Saudi Red, Funk, Indian White, Morgon 854, Morgon 856 and Pioneer 8ss in relation to water limitation. Seedlings of wheat and sorghum cultivars grown under water limitation showed increases in their stomatal density, epidermal cell density and trichome index in response to reduced watering frequency. Stomatal index of the two species, however, were not altered in the same way. In sorghum there was no apparent change in stomatal index in relation to water limitation treatment but stomatal density and trichome index increased. In wheat there was a marked reduction in the stomatal index in response to water limitation but there were increases in trichome indices and stomatal densities of all parts of the leaves. Wheat plants grown under water limitation imposed by polyethylene glycol (PEG) treatments to roots showed marked reductions in their growth compared with controls. Stomatal density was found to increase in response to PEG treatments while stomatal index decreased. Incubation of newly-germinated wheat seedlings in PEG resulted in an inhibition of growth of coleoptiles. However, the density of stomata decreased, unlike what was seen in leaf tissues. When wheat coleoptiles were subjected to conditions of limited water availability guard mother cell (GMC) production appeared not to be influenced by water status of the tissues. Wheat coleoptiles grown under different periods of light showed slight decreases in stomata density compared to the controls. Abscisic acid treatment was able to substitute for water limitation treatments by reducing stomatal index in both leaves and coleoptiles whilst increasing the production of trichomes in leaves. However, in coleoptile the same treatment reduced both the GMC index as well as stomata index. Salinity treatments, inhibited seed germination and were found to decrease stomatal index. Incubation of wheat seedlings in PEG resulted in a yellow pigmentation of the roots. The pigment was tentatively identified. However, it was not possible to distinguish whether the pigment was a specific metabolite of PEG in the roots or was produced by a non-biological conversion of PEG.

Thesis (Ph. D.)--University of Canterbury, 2009. / Typecript (photocopy). "December, 2009." Includes bibliographical references (p. 8-1 - 8-44). Also available via the World Wide Web.

Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2004. / "A dissertation in pharmaceutical sciences and chemistry." Advisor: Steven H. Neau. Typescript. Vita. Description based on contents viewed Feb. 24, 2006; title from "catalog record" of the print edition. Includes bibliographical references (leaves 129-141). Online version of the print edition.

Thesis (M.Ch.E.)--University of Delaware, 2005. / Principal faculty advisor: Abraham M. Lenhoff, Dept. of Chemical Engineering. Includes bibliographical references.

Presented diploma thesis deals with preparation of bioresorbable polyurethanes (PUR) and their characterization. The theoretical part describes the feedstocks used for the PUR preparation and summarizes the knowledge about PUR used in medical applications. Experimental part presents characterization of bioresorbable PUR films prepared by reactive casting in one step without the use of organic solvents. The absence of solvents represents a great advantage due to their toxicity and subsequent removal from the resulting product. The synthesis of PUR was conducted under an inert atmosphere by polyaddition reaction of hydrophobic poly(e-caprolactone) (PCL) and hydrophilic poly(ethylene glycol) (PEG) with hexamethylene diisocyanate (HDI). Synthesis under an inert atmosphere was necessary due to a side reaction of isocyanate with atmospheric humidity, which causes the formation of porous films instead of continuous ones. Prepared PUR films were characterized for different PCL/PEG ratios and different isocyanate index (ratio of NCO/OH reacted groups). PUR (isocyanate index 1.05) with PCL content 90 wt. % and higher demonstrated tought behavior in mechanical tests. Increase of isocyanate index and decrease of PCL content under 90 wt. % caused fragile sample behavior. The reason of such behavior was the different ability of PCL to crystallize in the structure of the polyurethane network. Increasing the PEG content has improved the ability of PUR films to absorb water and enhanced the rate of hydrolytic degradation. By adjusting the PCL/PEG ratio and the amount of isocyanate, solvent free bioresorbable PUR with suitable mechanical (flexibility, toughness) and physical properties (swelling, degradation) can be obtained. Prepared PUR films could be used in biomedicine e.g. as vascular grafts.