<p> A long-standing problem with the use of conventional cancer chemotherapy is the inherent lack of tumor specificity. Tumor-targeting drug-delivery systems (TTDS) have since been explored to overcome this deficiency. These drug conjugates can deliver potent cytotoxic drugs specifically to tumors and tumor cells with minimal systemic toxicity. Among various tumor-targeting molecules discussed, Designed Ankyrin Repeat Proteins (DARPins) represent a new approach to tumor targeting. In particular, DARPins targeting CD326 Epithelial Cell Adhesion Molecule (EpCAM) receptors provide an effective cancer target, as EpCAM is critical to the regulation of cellular matrix composition and overall cancer aggressiveness. </p><p> Botulism is a human illness caused by the bacterium <i>Clostridium botulinum</i> which results in fatal flaccid paralysis and eventual respiratory failure. <i>Clostridium botulinum</i> produces botulinum neurotoxins (BotNTs), which by themselves are considered by the CDC to be potential Category A bioterrorism weapons. The light chain protease domain of BotNTs efficiently cleaves SNARE proteins which in turn regulates neurotransmitter release in motor neurons, resulting in the inhibition of neuronal transmission. Discussed is the use of a novel footprint-based virtual screening to identify compounds with inhibitory activity against BotNTA-LC catalytic activity. </p><p> Fatty acid binding proteins (FABPs), have recently been identified as intracellular transporters for the endocannabinoid anadamide (AEA). Furthermore, animal studies by others have shown that elevated levels of endocannabinoids result in beneficial pharmacological effects on stress, pain and inflammation and also ameliorate the effects of drug withdrawal. Accordingly a novel &alpha;-truxillic acid derivative (SB-FI-26) was synthesized and assayed for its inhibitory activity against FABP5. Additionally, we found SB-FI-26 to act as a potent anti-nociceptive agent with mild anti-inflammatory activity in mice, which strongly supports our hypothesis that the inhibition of FABPs and subsequent elevation of anandamide is a promising new approach in drug discovery.</p>

This thesis describes the preparation, physico-chemical characterization and pharmacological studies of block copolymer micelles and vesicles for drug delivery applications. The incorporation and partition coefficients of model hydrophobic compounds (benzo[a]pyrene and Cell Tracker-DiI) are investigated in polycaprolactone-block-poly(ethylene oxide) copolymer micelles (PCL-b-PEO). The release of the probes is also studied from PCL-b-PEO micelles under perfect sink conditions. To investigate the usefulness of PCL-b-PEO micelles as a delivery vehicle for hydrophobic drugs, 17beta-estradiol (E2) is incorporated and released from the micelles. The biological activity of E2 is retained after micelle preparation and delivery to C57BL female mice. To investigate the cellular internalization of block copolymer micelles, gold labeled poly (4-vinylpyridine)- block-poly(ethylene oxide) micelles are internalized into A549 lung cells and HEK 293 kidney cells. The gold labeled P4VP-b-PEO micelles are visualized by transmission electron microscopy inside of endosomes and lysozomes of these cells. The incorporation and release of a hydrophilic drug, doxorubicin hydrochloride (DXR), into polystyrene-block-poly(acrylic acid) vesicles are investigated. An active pH loading method is used to incorporate DXR into the aqueous center of the vesicle. A plasticizer, dioxane is used to control the loading and release of DXR by tuning the permeability of the vesicle walls.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008. / Source: Dissertation Abstracts International, Volume: 69-11, Section: B, page: 6747. Adviser: Kenneth L. Watkin. Includes bibliographical references. Available on microfilm from Pro Quest Information and Learning.

Thesis (J.S.D.)--University of Illinois at Urbana-Champaign, 2009. / Source: Dissertation Abstracts International, Volume: 70-06, Section: A, page: . Adviser: Thomas Ulen. Includes bibliographical references (leaves 147-166) Available on microfilm from Pro Quest Information and Learning.

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