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Determination of the in vitro and in vivo oral drug delivery capabilities of complexation hydrogels /Perakslis, Eric D. Lowman, Anthony M. January 2006 (has links)
Thesis (Ph. D.)--Drexel University, 2006. / Includes abstract and vita. Includes bibliographical references (leaf 196).
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Synthesis and development of manufacturing processes for biopharmaceuticals /Fung, Ho Ki. January 2003 (has links)
Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references. Also available in electronic version. Access restricted to campus users.
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Chromatographic studies of drug-protein binding in diabetesJoseph, Kathryn (Krina) S. January 2010 (has links)
Thesis (Ph.D.)--University of Nebraska-Lincoln, 2010. / Title from title screen (site viewed July 8, 2010). PDF text: x, 259 p. : ill. (chiefly col.) ; 4 Mb. UMI publication number: AAT 3398195. Includes bibliographical references. Also available in microfilm and microfiche formats.
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Effect of secondary structure on paracellular transport of polypeptidesChittchang, Montakarn, Johnston, Thomas P. January 2004 (has links)
Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2004. / "A dissertation in pharmaceutical sciences and chemistry." Advisor: Thomas P. Johnston. Typescript. Vita. Description based on contents viewed Feb. 23, 2006; title from "catalog record" of the print edition. Includes bibliographical references (leaves 202-223). Online version of the print edition.
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Oral delivery of protein-transporter bioconjugates using intelligent complexation hydrogelsShofner, Justin Patrick, January 1900 (has links)
Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.
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Oral delivery of protein-transporter bioconjugates using intelligent complexation hydrogelsShofner, Justin Patrick, 1983- 02 October 2012 (has links)
Several polymer systems including P(MAA-g-EG) and P(MAA-co-NVP) with crosslinking agents TEGDMA and PEGDMA1000, monomer-to-solvent ratios of 67:33, 60:40, and 50:50, and particle sizes of <75 microns, 90-150 microns, and 150-212 microns were synthesized for use with protein-transporter conjugates. All synthesized systems were characterized by SEM which demonstrated the visual size, surface features, and surface textures of the polymer microparticles. Insulin-transferrin and calcitonin-transferrin conjugates were successfully synthesized using the protein crosslinker SPDP, binding the two proteins with a disulfide bond. The multi-step conjugation reactions used to create the conjugates were analyzed by the use of UV spectroscopy and HPLC to ensure the quality of the final products. In both conjugation reactions, the final product yield was found to be over 70%. The in vitro loading and release characteristics for insulin-transferrin and calcitonin-transferrin were separately investigated. By testing loading and release using a number of different polymer systems with different synthesis parameters, it was possible to optimize the hydrogel carriers for use with each of the conjugates independently. Upon optimization, the ideal system for use with insulin-transferrin and calcitonin-transferrin was found to be P(MAA-g-EG) microparticles of <75 microns formed using a PEGDMA1000 crosslinker and a 50:50 monomer-to-solvent ratio for both conjugates through separate optimization processes. This optimized polymer carrier was found to release upwards of 50% of loaded insulin-transferrin conjugate and near 90% of loaded calcitonin-transferrin conjugate. The insulin-transferrin conjugate was further evaluated through the use of cellular and animal models. Using cellular models, the insulin-transferrin conjugate was shown to increase transport relative to insulin by a factor of 7, achieving an apparent permeability of 37 x 10⁹ cm/s. Also, in the presence of polymer microparticles, the insulin-transferrin conjugate increased transport by a factor of 14 times relative to insulin, achieve an apparent permeability of 72.8 x 10⁹ cm/s. The presence of the microparticles near the cells was found to improve conjugate transport by nearly 100%. The preliminary animal studies verified the successful synthesis of the insulin-transferrin conjugate as well as demonstrated the bioactivity of the insulin portion of the molecule by achieving a drop in blood glucose level upon subcutaneous injection. / text
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The comparison of biological properties of L- and D-enantiomeric antimicrobial peptidesKwok, Hoi-shan, 郭凱珊 January 2014 (has links)
Antibiotics have been used widely for the treatment of bacterial infections for over half a century. However, the emergence of resistance to antibiotics has aroused public health concern, leading to the development of antimicrobial peptides (AMPs) as potential alternative therapeutic agents against bacterial infections. AMPs are naturally found in many species and have important roles in our innate immune defense systems. AMPs are usually cationic amphipathic peptides with membrane destabilizing property. They have a relatively broad spectrum of antimicrobial activity and pathogens are less likely to develop resistance against AMPs. The major challenge of using AMPs as therapeutic agents is their toxicity towards mammalian cells. The biological stability of AMPs to protease in human body is another concern.
To address the latter problem, instead of the naturally occur L-enantiomers, Denantiomeric AMPs were introduced to enhance their stability. This study aimed to test the hypothesis that the D-enantiomeric AMPs are more resistant than the Lenantiomeric AMPs against proteolytic degradation. Three pairs of synthetic D-/LAMPs (D-LAO160-P13/LAO160-P12; D-LAO160-H/LAO160-H; and D-LAK-120-HP13/LAK-120-HP13) were employed to test for their stability when treated with trypsin, serum and gastric fluid, and the samples were analyzed by high performance liquid chromatography (HPLC). Generally, all the D-enantiomeric AMPs were found to be resistant towards proteolysis. Besides, to compare the cytotoxicity of D-/LAMPs, MTT and LDH assays of the D/L-LAK120-HP13 pair were carried out on two different cell lines, A549 cells (human lung adenocarcinoma epithelial cells) and RAW264.7 cells (mouse macrophage cells). Significant difference in cytotoxicity of D-LAK120-HP13 and LAK120-HP13 on RAW264.7 cells were obtained from MTT assay, but not in LDH assays or on A549 cells. Further analysis has to be done to validate the findings obtained from this research. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences
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Amphibian antimicrobial peptides : their structures and mechanisms of action : a thesis presented for the degree of Doctor of Philosophy / by Brian Cheng San Chia.Chia, Brian Cheng San January 2000 (has links)
Copy of author's previously published works inserted. / Bibliography: leaves 183-220. / xiii, 226 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Three antimicrobial peptides, maculatin 1.1, uperin 3.6 and caerin 4.1 have been isolated from the respective skin glands of the Australian amphibians Litoria genimaculata, Uperoleia mjobergii and Litoria caerulea. To gain a deeper insight into their mechanisms of action, three dimensional structural studies have been conducted using circular dichroism, two-dimensional nuclear resonance and computer modelling techniques. The role of central flexibility within antibiotic peptides in their interaction with bacterial membranes is also discussed. / Thesis (Ph.D.)--University of Adelaide, Dept. of Chemistry, 2000
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Chemistry and medical implications of novel amphibian peptides : a thesis submitted for the degree of Doctor of Philosophy /Wabnitz, Paul Andrew. January 1999 (has links) (PDF)
Thesis (Ph.D.) -- University of Adelaide, Dept. of Chemistry, 2000. / Copies of author's previously published articles inserted. Includes bibliographical references.
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Amphibian antimicrobial peptides : their structures and mechanisms of action : a thesis presented for the degree of Doctor of Philosophy /Chia, Brian Cheng San. January 2000 (has links) (PDF)
Thesis (Ph.D.)--University of Adelaide, Dept. of Chemistry, 2000. / Copy of author's previously published works inserted. Bibliography: leaves 183-220.
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