Medicine and Health Sciences Commons^™

Development Of Oral Vaccines Against Lyme Disease, Rita Raquel Dos Anjos De Carvalho E Melo

Theses and Dissertations (ETD)

Lyme Disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. If left untreated, it can lead to permanent damage to the nervous and musculoskeletal systems. In some cases, patients that receive the recommended antibiotic therapy develop a debilitating health condition associated with substantial health care costs. Despite current preventive measures, the incidence and the geographic distribution of Lyme Disease continues to increase. Recent estimates from CDC suggest that the true number of cases of Lyme Disease in the US is approximately 300,000 per year. Yet, there is currently no vaccine …

Optimization Of Lead Spectinamide Compounds As Novel Anti-Tuberculosis Agents With A Pharmacometric Approach, Ashit Rasendu Trivedi

Theses and Dissertations (ETD)

In an effort to combat the global Tuberculosis pandemic, Dr.Richard E. Lee and his group at St.Jude Children’s Research Hospital designed a novel series of anti-tuberculosis agents, spectinamides – semi-synthetic analogs of spectinomycin. Spectinamides are a potent inhibitor of mycobacterial ribosomes and overcome efflux mediated drug resistance in M. tb. Spectinamides have shown an excellent in vitro activity, which makes them well suited for further lead optimization and preclinical development. We hypothesized that through pharmacokinetic (PK) and pharmacodynamics (PD) model-based dosing optimization studies, we could strategically guide the selection and refinement of more potent and effective anti-TB spectinamides. Biopharmaceutical in …

Development And Evaluation Of Amphotericin B Loaded Iron Oxide Nanoparticles For Targeted Drug Delivery To Systemic Fungal Infections, Pavan Balabathula

Theses and Dissertations (ETD)

A targeted nanotheronostic drug delivery system to diagnose and treat life threatening invasive fungal infections (IFIs) such as cryptococcal meningitis was designed, developed, characterized, and evaluated. To address the development processes, first, iron oxide nanoparticles (IONP) (34-40 nm) coated with bovine serum albumin (BSA), loaded and targeted with amphotericin B (AMB) (AMB-IONP) was formulated by applying a layer by layer approach. Several designs (A, B, C, D, & E) of AMB-IONP were developed and their physicochemical properties such as drug loading with HPLC method, particle size, poly dispersity index (PDI), and ζ-potential using dynamic light scattering (DLS) technique, morphology with …

Discovery Of Novel Tubulin Polymerization Inhibitors And Survivin Inhibitors As Potential Anticancer Agents, Min Xiao

Theses and Dissertations (ETD)

Melanoma is the most dangerous form of skin cancer and accounts for the majority of skin cancer death. Although considerable advances have been made in melanoma treatment in recent years, there are many problems associated with current therapies. Drug resistance to targeted therapies is almost inevitable after short term treatment. Immunotherapies generally have low response rate and the effects vary among patients. Therefore, the need to develop new and more effective treatment for melanoma is high.

The work presented here focuses on discovery of novel anticancer agents for melanoma by targeting two important cancer targets: tubulin and survivin. Microtubules play …

Challenges In The Pharmacokinetics Of Therapeutic Proteins, Wararat Limothai

Theses and Dissertations (ETD)

Due to the complex structure and complicated disposition pattern of therapeutic macromolecules, their pharmacokinetic interpretation has many challenges. Two of these challenges were investigated in this dissertation: 1) the error of classical bioavailability assessment observed during subcutaneous (SC) administration of therapeutic macromolecules that undergo target-mediated drug disposition (TMDD) and 2) the ontogeny of the neonatal Fc receptor (FcRn) expression along with its effect on the pharmacokinetics of monoclonal antibodies (mAbs) during development.

TMDD often well describes the pharmacokinetics of therapeutic proteins that have high specificity and affinity of binding to their target receptors. The target receptors can be saturated by …

Overcoming Acquired Resistance To Braf Inhibitors By Novel Synergistic Drug Combination And Discovery Of Novel Smac Mimetics As Selective Survivin Inhibitors, Jin Wang

Theses and Dissertations (ETD)

The first part (Chapter 1 and 2) of this dissertation presents a novel combination study of melanoma therapy. Acquired clinical resistance to vemurafenib, a selective BRAFV600E inhibitor, arises frequently after short term chemotherapy. Since the inhibitions of targets in the RAFMEK-ERK pathway result in G0/G1 cell cycle arrest, vemurafenib-resistant cancer cells are expected to escape this cell cycle arrest and progress to subsequent G2/M phase. We hypothesized that a combined therapy using vemurafenib with a G2/M phase blocking agent will trap resistant cells and overcome vemurafenib resistance. To test this hypothesis, we first determined the combination index (CI) values of …

Research Proposal: Emrs Changing Patient Medication Errors, Kerry Moore

Applied Research Projects

In 2009 the federal government initiated the American Recovery and Reinvestment Act (ARRA) in efforts to improve timely and quality health care. This new initiative promised to provide great incentives to health care providers who took advantage of the program by implementing electronic medical records (EMRs) within their facilities, clinics, and practices. Coupled with tight deadlines and the incentive of reimbursement, the health care world has been witness to an influx of EMRs being developed by vendors and implemented at health care facilities. The rate at which these EMRs have been implemented has been astounding. So fast, the health care …

The Value Of Online Medication Rating Systems To Older Adults And Their Association With Self-Reported Outcomes, Yazed Sulaiman Alruthia

Theses and Dissertations (ETD)

The Internet is a powerful and very popular vehicle for distributing judgment-free health information to patients. Multiple studies have examined the role of online health information as well as physician-rating websites in health care. Studies have examined the value of online drug information for patients and the value of the online drug information for patients. However, no study has examined the usefulness or value of online medication rating websites in facilitating physician-patient communication or participant-reported outcomes. In this study, the value of online medication rating websites to older adults in facilitating communication with their physicians using a newly developed tool …

Design, Development And Evaluation Of Erlotinib-Loaded Hybrid Nanoparticles For Targeted Drug Delivery To Nonsmall Cell Lung Cancer, Bivash Mandal

Theses and Dissertations (ETD)

The objective of this work was to design, develop and evaluate erlotinib-loaded coreshell type lipid albumin hybrid nanoparticles (CSLAHNPs) for targeted drug delivery to nonsmall cell lung cancer (NSCLC). Erlotinib (ETB) is a highly selective, potent and reversible inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR) which is overexpressed (50-90%) in NSCLC. ETB is marketed as film coated tablets for oral delivery. However, poor survival rate along with life-threatening adverse effects were reported from oral administration. Nanoparticulate delivery system of ETB might be advantageous to target the tumor cells, thereby increasing therapeutic efficacy and reducing off-targeting toxicities of ETB …

Functional Activity And Switching Of Novel Cannabinergic Ligands, Bret Alan Koertge

Theses and Dissertations (ETD)

Pursuant to the discovery of the cannabinoid receptors, research in this field has grown exponentially over the last 2 decades. With their utility in various disease states such as heart disease, cancer, stroke, neurodegenerative and inflammation, cannabinoids stand poised to become a great therapeutic agent. This research seeks to better understand the functional mechanism of cannabinoids, in the hopes of ascertaining which molecular attributes confer desirable selectivity and functional activity.

Looking first at classical benzchromene core analogues, we have shown that presence of an aromatic substitution at C-1' imparts a CB1 agonist, CB2 antagonist. This is a unique mechanism and …

Design, Development, Characterization And Testing Of Cd22 Targeted Long Circulating Liposomal Drug Delivery Systems For B Cell Malignancies, Nivesh Kumar Mittal

Theses and Dissertations (ETD)

Hematological malignances of the B cells affect almost 130,000 people in the United States every year of which approximately 44,000 lose their lives. Therapies for B cell malignancies such as doxorubicin, have limitations due to dose related adverse effects such as neutropenia and cardiomyopathy. AD 198 is a novel PKC-delta activating agent that has cytotoxic superiority over doxorubicin by being able to circumvent resistance mechanisms developed by the cancer cells towards doxorubicin and being cadioprotective from the damage caused to cardiomyocytes by doxorubicin. Targeted delivery of AD 198 is crucial to moderate the non-specific interactions of the chemotherapeutic agent with …