Life Sciences Commons^™

Design And Synthesis Of Enzalutamide-Isothiocyanate Hybrid Drug As Anti-Prostate Cancer Agent, Siyu Ou

Wayne State University Theses

Isothiocyanate (ITC), such as sulforaphane (SFN), is an active metabolite of dietary glucosinolate from cruciferous vegetables. SFN-rich extracts have been recently tested in recurrent prostate cancer (PCa) patients and notably prolonged PSA doubling time without Grade 3 adverse events. One of the anti-PCa mechanisms of SFN is to inhibit HDAC6, which further triggering androgen receptor (AR) degradation. We have incorporated ITC to the chemical scaffold of enzalutamide (Enz) to create Enz-ITC hybrid molecules with an intention to intracellularly deliver ITC to AR-Hsp90-HDAC6 complex and therefore improving anti-PCa efficacy of both parental drugs. Two Enz-ITCs and one Enz-ITC N-acetyl cysteine (NAC) …

Targeted Delivery Of Nrf2 Sirna Using Modular Polymeric Micellar Nanodelivery System For Efficient Target Gene Knockdown In Hepatocellular Carcinoma, Shaimaa Mohamed Ibrahim Yousef

Wayne State University Theses

Tumor selective drug delivery as well as chemotherapy associated multi drug resistance (MDR) pose tremendous hurdles for effective cancer therapy. In this regard, designing multifunctional nanocarriers loaded with drug/gene payloads and engineered with tumor targeting ligands can serve as a modular platform for targeted drug/gene delivery. In this study we undertook the synthesis of a self-assembling block copolymer constructed using poly(styrene-co-maleic anhydride, partial iso-octyl ester) (SMAPIE) and branched polyethylenimine (PEI) as building blocks and evaluated its micelle forming ability, siRNA complexation and siRNA delivery potentials. In addition, we engineered galactosamine decorated nanomicelles using modular “click” chemistry based approaches for evaluating …

Dendrimer-Coated Iron Oxide Theranostic Nanoparticles For Cancer Imaging And Therapy, Duy Khanh Luong

Wayne State University Theses

The bleak prognosis for patients diagnosed with metastatic cancer along with the low therapeutic efficacy and the recurrence of cancer in conventional chemotherapy are prompting clinical medicine to adopt a new strategy to detect cancer in early stage and to deliver the anticancer drugs specifically to tumor site to enhance therapeutic efficiency and minimize side effects. The aim of this study is to design a theranostic nanocarrier consisting of iron oxide nanoparticles (SPIONs) for magnetic resonance imaging (MRI) and Polyamidoamine dendrimers conjugated with folic acid (FA-PAMAM) for active targeted delivery of a highly potent but extremely lipophilic anticancer compound 3,4-difluorobenzylidene …

Development Of A Dreissena Bioassay To Assess The Toxicity Of Contaminants Across Two Life-History Stages, Caroline Joyce Addis

Wayne State University Theses

Dreissenid mussels (Dreissena polymorpha and D. bugensis) have rapidly become widespread and ubiquitous in North America since their introduction into the Great Lakes in the 1980s. The resulting environmental and economic impacts of their invasion have been extensive, negatively affecting biodiversity and costing millions of dollars in control efforts and damage to power generation and water treatment facilities. Although dreissenids are often associated with negative impacts, they may present a practical tool for toxicology studies. The typically sessile behavior of the benthic adults coupled with the planktonic nature of the veligers allow for a more complete evaluation of water quality …

Impact Of Cefazolin Co-Administration With Vancomycin To Reduce Development Of Vancomycin Intermediate Staphylococcus Aureus, Nivedita Birbahadur Singh

Wayne State University Theses

IMPACT OF CEFAZOLIN CO-ADMINISTRATION WITH VANCOMYCIN TO REDUCE DEVELOPMENT OF VANCOMYCIN INTERMEDIATE STAPHYLOCOCCUS AUREUS

by

NIVEDITA B SINGH

August 2106

Advisor: Dr. Michael J. Rybak

Major: Pharmaceutical sciences

Degree: Masters of Science

Objective: Development of resistance in S. aureus has been a big concern in the treatment of infections caused by the organism. The line of therapy used today has a disadvantage of slowly developing cross-resistance for antibiotics such as DAP secondary to prior VAN exposure. Therefore, alternative therapy is needed to prevent the emergence of VAN resistance and cross-resistance to other antibiotics. The primary aim of this experiment is …