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A dissertation presented in fulfillment of part of the requirements for the degree of Master of Medicine (Pathology) in the Faculty of Medicine, University of the Witwatersrand, Johannesburg, November, 1966. / WHSLYP2017

Thesis (Ph. D.)--Florida State University, 2005. / Advisor: Qing-Xiang A. Sang, Florida State University, College of Arts and Sciences, Dept. of Chemistry and Biochemistry. Title and description from dissertation home page (viewed May 11, 2006). Document formatted into pages; contains xvii, 118 pages. Includes bibliographical references.

No description available.

Part I. Following a general historical review of the development of drug targeting, critical evaluations were made of current targeted drug delivery systems. Based on the results shown by previous studies, magnetic albumin microspheres containing adriamycin is one of the most promising targetable delivery systems for the treatment of solid tumors. It was also apparent that the pharmacokinetics of drugs associated with magnetic albumin microspheres had not been determined. A systematic study of the multiple variables involved in albumin microsphere preparation was completed to identify to what extent these variables affected the microsphere size distribution. The results of this investigation led to an optimal method of microsphere preparation. Information obtained from the above studies was applied to the production of magnetic albumin microspheres containing adriamycin suitable for in vivo use. The problems of separation and quantitation of adriamycin and adriamycinol in biological matrices were investigated using ion-pairing high pressure liquid chromatography. An optimized chromatographic system was presented for the analysis of these compounds in rat serum and tissues. The disposition of adriamycin following administration as magnetic albumin microspheres and as a solution was studied by monitoring adriamycin concentrations in multiple rat tissues for forty-eight hours after administration. The magnetic dosage form was targeted to a predefined tail segment with a magnetic field strength of 8000 G applied for 30 min after dosing. A physiological pharmacokinetic model was used to describe the disposition of adriamycin after both dosage forms. The model developed following adriamycin administration as a solution served as the foundation for the model for adriamycin when it was administered as the magnetic dosage form. Part II. The present investigation was designed to characterize the kinetics of ibuprofen in plasma and synovial fluid, which in the past, has been flawed by inadequate study protocols. After administration of a single dose and at steady-state, ibuprofen concentrations were measured simultaneously in plasma and synovial fluid obtained from eight patients with rheumatoid arthritis. The extent of accumulation of ibuprofen in each fluid was determined. The degree of ibuprofen protein binding in plasma and synovial fluid was also determined and related to its kinetic behavior.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Due to the high affinity and selectivity of aptamer selected from DNA library towards target proteins, the use of specific protein biomarkers to assist early diagnosis, and the recent rapid development of piezoelectric quartz crystal (PQC) biosensor technology, the research reported is focused on developing PQC biosensor using aptamers selected from a DNA library as selective coating for the detection of albumin in urine, two protein biomarkers for malaria in sera, and the determination of trace amount of SCV helicase protein from SAR in sera. Three new aptamer-PQC biosensors are developed with research conducted on aptamer selection, optimization of coating methods for aptamers on PQC, and coupling paramagnetic nanoparticle technology with PQC biosensor in flow injection analysis (FIA) to enrich analyte and eliminate sample matrix interference. A new approach for aptamer selection is successfully attempted in the development of the first aptamer-PQC biosensor with an aim to offer an early detection of microalbuminuria enabled by an increase in detection sensitivity with aptamer selected by its actual binding with albumin-PQC biosensor. The aptamer-PQC sensor developed has shown to give a working range between 0.1 to 10 ug/mL, a detection limit (S/N = 3, n=3) of 0.048 μg/ml, repeatability of RSD = 6.8% (n=3), a response time of 1 minute and a throughput of 60 samples/hour. The developed piezoelectric aptamer sensor is shown to have sufficient sensitivity to detect microgram quantities of albumin in urine. Aptamer-PQC biosensors are developed for the detection of two protein biomarkers, PfLDH for general diagnosis and PfHRP-2 for a specific diagnosis of Plasmodium falciparum malaria parasitemia, in sera. The results show satisfactory working range from 10-100 ng/mL for both PfLDH and PfHRP-2 protein biomarker, low detection limit of 1.8 and 4.7 ng/mL and satisfactory repeatability (%RSD, n = 3) of 7.4% and 9.2% for PfHRP-2 and PfLDH respectively. It is first report for aptamer based PQC biosensor to detect malarial PfHRP-2 and PfLDH at ppb range to meet the requirement for their diagnosis. To meet the highly demanding challenge for detecting protein biomarkers at pg/mL level in high-protein sera sample, the coupling of paramagnetic nanoparticle technology with aptamer-PQC biosensor was attempted for developing aptamer-PQC biosensor for selective detection of SCV helicase protein produced from SARS CoV replication. The coupling of aptamer coated paramagnetic nanoparticles for sample pretreatment to aptamer-PQC biosensor has shown to detect helicase protein in one-minute assay with a detection limit of 350 pg/mL. The aptamer-coated crystal exhibits a frequency shift linearly proportional to the concentration of SARS helicase from 1 to 1000 ng/mL with a correlation coefficient of 0.9975 and a repeatability of 6.8% (%RSD, n=3). After the enrichment procedure, recoveries of 102% and 119% were achieved using samples spiked with SARS helicase at concentrations of 10 ng/mL and 1.0 ng/mL respectively. It is the first report to detect for SCV helicase protein using PQC biosensor at pg/mL level after magnetic bead enrichment. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Thesis (M.Sc.). / Written for the Dept. of Bioresource Engineering. Title from title page of PDF (viewed 2007/08/30). Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references. Also available in print.

Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 205-214). Also available on the Internet.