Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xvi, 169 p.; also includes graphics (some col.) Includes bibliographical references (p. 155-169). Available online via OhioLINK's ETD Center

Lo Ho Yin. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 142-149). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Lee Chi-man. / "July 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Paclitaxel is a very important anticancer drug commonly called Taxol®. We know from previous work (Hoffman, et al., 1998) that Taxol exists in filbert, Corylus avellana L. material. Quantification of Taxol in filbert plant material is painstaking and hitherto was accomplished by rapidly processing single batches in a complicated procedure (Hoffman, et al., 1998), which seemingly unavoidably, was accompanied by some degradation. However for extraction, testing, plant physiological and horticultural purposes a simplified method of determining Taxol yield is required. All simplified methods tested were found limited by rapid degradation of Taxol. Under these conditions not only is the sought product broken down, but we were unable to distinguish Taxol precursors from degradation products. Thus it was decided to go back to first principles and study the degradation of Taxol in vitro. Degradation kinetics of Taxol was studied using electrospray ionization mass spectrometry (ESIMS) to identify possible Taxol adducts and degradation products. Our preparation for ESIMS analysis by experimental necessity involved various other components. Since some of these components interacted with the degradation products, we developed a program to distinguish these putative adducts from spurious components found in the system and we were able to plot the pH dependence of Taxol degradation in this system at room temperature (approximately 25oC). The results of the mass spectrometric analysis of these degradants were found dependent on pH and time. Our results show major degradation at pH 9 and beyond, plus minor degradation at pH 5. Two optimum pHs for stability were found at pH 4 and pH 7. This data varies slightly from the published results Dordunoo and Burt (1996). Our smoother curves define two pHs events in this pH range which to our knowledge, have not been reported and our temperature was lower. We hope that this information will help us extract Taxol more efficiently with greater yield from novel plant sources, e.g. hazel (filbert) tree, Corylus avellana L. The possibility of Taxol dimer formation in solution and perhaps in vivo can be inferred, but not proven, in this work. This dimer, may exist, in dynamic equilibrium with parent compound, Taxol. / Graduation date: 2006

For the first time, two distinct, well-characterized water-soluble chemotherapeutic-C60 conjugates have been constructed for targeted drug delivery of paclitaxel to cancer cells. In vitro work was carried out in two stages to determine IC50 values of the conjugates. Primarily, work was carried out on A375m melanoma, T-24 bladder carcinoma, and Hep 3B hepatocellular carcinoma cell lines. In these studies, it was revealed that although the first compound, a paclitaxel-2’-succinate-C60 derivative, experienced a dramatic loss of cytotoxicity in comparison to paclitaxel, the second derivative, utilizing a poly(ethylene glycol) linker, demonstrated over 10× better cytotoxicity than paclitaxel itself. Additional in vitro studies were carried out for the purpose of creating a chemotherapeutic-fullerene-monoclonal antibody immunoconjugate for targeted drug delivery. Building on our previous work, supermolecular forces, instead of covalent chemical bonding were used to associate antibodies with the paclitaxel-2’-succinate-C60 derivative to construct an immunoconjugate. While cytotoxicity was measurable, no discernible advantage was seen by the targeted C60-(ZME-018) immunoconjugate over a MuIgG control, thus leaving room for further refinement of the approach for targeted cancer therapy. In vivo work, using the potent paclitaxel-poly(ethylene glycol)-C60 derivative in a murine model, demonstrated success by producing a similar capacity for tumor-reduction compared to the FDA-approved drug Abraxane®, without the associated weight-loss in animals seen for Abraxane. A major contribution of this work is the progress made toward development of Fullerene Immunotherapy (FIT) and the potential translation of FIT into the clinic. Having demonstrated the potent, improved cytotoxicity of a paclitaxel-C60 conjugate, the next step in the development of FIT is the successful construction of a therapeutic fullerene-antibody immunoconjugate. The results documented in this work have now shifted the onus of FIT from a theoretical concept to a realistic goal awaiting final developmental refinement.

Thèse d'exercice : Pharmacie : Université de Nantes : 2003. / Bibliogr. f.104-112 [73 réf.].

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 150-163).

No description available.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 6 uppsatser.

Thesis (Ph. D.)--State University of New York at Binghamton, Dept. of Chemistry, 2007.