Pharmacy and Pharmaceutical Sciences Commons^™

Nose To Brain Delivery Of Therapeutic Agents, Siva Ram Kiran Vaka

Electronic Theses and Dissertations

The potential treatment approaches for various disorders associated with central nervous system are invasive and do not allow frequent administration. Brain targeting of drugs by intranasal route is a safe and noninvasive method of drug delivery which allows frequent administration and is certainly more patient compliant than the currently folloinvasive methods. In this study, the plausibility of delivering neurotrophins [nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF)], neurotrophinogenic agents (ex: carnosic acid) and antibiotics (ex: cefotaxime) to brain via nose-brain pathway using chitosan as barrier modulating agent was investigated. In vitro permeation studies of fluorescein isothiocyanate dextran (FD40k) …

Geriatric Care As An Introductory Pharmacy Practice Experience, Joseph A. Woelfel, Eric Boyce, Rajul A. Patel

School of Pharmacy Faculty Articles

Objective. To describe the design, delivery, and impact of a geriatric introductory pharmacy practice experience (IPPE) to develop students’ skills related to consultant pharmacists’ roles and patient care responsibilities.

Design. A required 2-unit geriatric IPPE, involving 40 hours in a geriatric-care facility, 5 reflection hours, and 12 classroom-discussion hours, was developed for first- and second-year pharmacy students. Students interviewed patients and caregivers, reviewed patient charts, triaged patient needs, prepared care plans, and performed quality-assurance functions.

Assessment. After completing the IPPE, students’ geriatric- and patient-care abilities were enhanced, based on review of their interactions, care plans, reflections, and examinations, and they …

An Examination Of Awareness Of Over-The-Counter Nonsteroidal Anti-Inflammatory Drugs And Adverse Events, Michelle Popa

Walden Dissertations and Doctoral Studies

The elderly population is among the fastest growing populations in the United States. Finding and consuming medications safely and effectively are challenging endeavors for this population. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a widely consumed class of medications among the elderly population, with 70% of individuals consuming over-the-counter (OTC) NSAIDs once a week and 34% using them daily. The purpose of this quantitative study was to determine whether (a) patients are aware of the risks associated with the consumption of NSAIDs, and (b) there are differences in awareness based upon specific demographic characteristics and levels of patient-physician communication. The health belief …

An Evidence-Based Review Of Fat Modifying Supplemental Weight Loss Products., Amy M Egras, William R Hamilton, Thomas L Lenz, Michael S Monaghan

College of Pharmacy Faculty Papers

Objective. To review the literature on fat modifying dietary supplements commonly used for weight loss. Methods. Recently published randomized, placebo-controlled trials were identified in PubMed, MEDLINE, International Pharmaceutical Abstracts, Cochrane Database, and Google Scholar using the search terms dietary supplement, herbal, weight loss, obesity, and individual supplement names. Discussion. Data for conjugated linoleic acid (CLA), Garcinia cambogia, chitosan, pyruvate, Irvingia gabonensis, and chia seed for weight loss were identified. CLA, chitosan, pyruvate, and Irvingia gabonensis appeared to be effective in weight loss via fat modifying mechanisms. However, the data on the use of these products is limited. Conclusion. Many obese …

Opioid Codrugs For Pain Management, Ujjwal Chakraborty

Theses and Dissertations--Chemistry

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissus damage or described in terms of such damage. Opioids are effective in treating moderate to severe pain, but opioid alone therapy is associated with several adverse effects, development of tolerance and addiction potential. One way to solve these problems is to administer opioids with adjuvant drugs. In this project several opioid molecules were combined with other adjuvant drugs in a single chemical entity to form a codrug.

A series of codrugs were prepared by conjugation of an opioid with S-(-)-nornicotine, ketamine, norketamine and gabapentin. Several …

Cathepsin B: A Potential Prognostic Marker For Inflammatory Breast Cancer, Mohamed A. Nouh, Mona M. Mohamed, Mohamed El-Shinawi, Mohamed A. Shaalan, Dora Cavallo-Medved, Hussein M. Khaled, Bonnie F. Sloane

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; however, very little is known about its role in IBC.

Methods

In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found that CTSB is localized to caveolar membrane microdomains in cancer cell lines including IBC, and …

Inhibition Of Cathepsin B Activity Attenuates Extracellular Matrix Degradation And Inflammatory Breast Cancer Invasion, Bernadette C. Victor, Arulselvi Anbalagan, Mona M. Mohamed, Bonnie F. Sloane, Dora Cavallo-Medved

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

Inflammatory breast cancer (IBC) is an aggressive, metastatic and highly angiogenic form of locally advanced breast cancer with a relatively poor three-year survival rate. Breast cancer invasion has been linked to proteolytic activity at the tumor cell surface. Here we explored a role for active cathepsin B on the cell surface in the invasiveness of IBC.

Methods

We examined expression of the cysteine protease cathepsin B and the serine protease urokinase plasminogen activator (uPA), its receptor uPAR and caveolin-1 in two IBC cell lines: SUM149 and SUM190. We utilized a live cell proteolysis assay to localize in real …

Biochemical Evaluation Of Lignin-Like Molecules, Jay Thakkar

Theses and Dissertations

Current anticoagulants carry a serious risk of bleeding complications. In addition, narrow therapeutic index, drug interactions, immunological reactions, toxicity and high cost to benefit ratio limits the effective use of these drugs in patients with thrombotic conditions.Heparin is the most widely used anticoagulant. We hypothesized that one of the major drawback of heparins, its non-specific interaction with the plasma proteins arises as a result of negative charges. To reduce these non-specific interactions, our laboratory designed sulfated low molecular weight lignin (LMWL) like biomacromolecules, which were found to be direct inhibitors of thrombin and factor Xa, acting through a unique exosite-2 …

“Clicked” Bivalent Multifunctional Ligands In Alzheimer’S Disease., Ronak Gandhi

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by beta-amyloid (Aβ) aggregation/oligomerization, biometal dyshomeostasis, oxidative stress, and neuroinflammation. The multifactorial nature of AD may indicate the therapeutic potential of multifunctional ligands that tackle various risk factors simultaneously as effective AD-modifying agents. This notion is further supported by the fact that while numerous AD-modifying agents targeting one single risk factor have been developed and a number of them entered clinical trials, none of them has been successfully approved by the FDA. Furthermore, neuronal cell membrane/lipid rafts (CM/LR) have been demonstrated to associate with all the indicated risk factors, indicating that this …

Atomic Force Microscopy Method Development For Surface Energy Analysis, Clare Aubrey Medendorp

University of Kentucky Doctoral Dissertations

The vast majority of pharmaceutical drug products are developed, manufactured, and delivered in the solid-state where the active pharmaceutical ingredient (API) is crystalline. With the potential to exist as polymorphs, salts, hydrates, solvates, and cocrystals, each with their own unique associated physicochemical properties, crystals and their forms directly influence bioavailability and manufacturability of the final drug product. Understanding and controlling the crystalline form of the API throughout the drug development process is absolutely critical. Interfacial properties, such as surface energy, define the interactions between two materials in contact. For crystal growth, surface energy between crystal surfaces and liquid environments not …

Isolation And Elucidation Of The Chrysomycin Biosynthetic Gene Cluster And Altering The Glycosylation Patterns Of Tetracenomycins And Mithramycin-Pathway Molecules, Stephen Eric Nybo

University of Kentucky Doctoral Dissertations

Natural products occupy a central role as the majority of currently used antibiotic and anticancer agents. Among these are type-II polyketide synthase (PKS)-derived molecules, or polyketides, which are produced by many representatives of the genus Streptomyces. Some type-II polyketides, such as the tetracyclines and the anthracycline doxorubicin, are currently employed as therapeutics. However, several polyketide molecules exhibit promising biological activity, but due to toxic side effects or solubility concerns, remain undeveloped as drugs.

Gilvocarcin V (GV) (topoisomerase II inhibitor) has a novel mechanism of action: [2+2] cycloaddition to thymine residues by the 8-vinyl side chain and cross-linking of histone …

The Absence Of Abcd2 Reveals A Novel Role For Peroxisomes In The Protection From Metabolic Syndrome, Jingjing Liu

University of Kentucky Doctoral Dissertations

ABCD2 (D2) is a peroxisomal ATP binding cassette (ABC) transporter that is expressed in brain, adrenal and liver. D2 is transcriptionally regulated by key transcriptional factors that control lipid and glucose metabolism. Therefore, we examined its role in adipose tissue. These studies revealed that D2 is highly abundant in adipose tissue and upregulated during adipogenesis. However, D2 deficiency does not affect either adipogenesis or lipid accumulation. An examination of the lipid profile of adipose tissue revealed the accumulation of C20 and C22 fatty acids in D2 deficient (D2‐/‐) mice. When challenged with a diet enriched in erucic acid (C22:1, 10% …

Microneedle-Assisted Transdermal Delivery Of Naltrexone Species: In Vitro Permeation And In Vivo Pharmacokinetic Studies, Mikolaj Milewski

University of Kentucky Doctoral Dissertations

Naltrexone (NTX) is a drug used primarily in the management of alcohol dependence and opioid dependence. Based on several drawbacks associated with the oral and injectable intramuscular dosage forms of naltrexone currently available on the market, there is substantial interest in delivering naltrexone transdermally. Although naltrexone does not permeate skin at the rate sufficient to reach therapeutic plasma concentrations in humans, novel flux enhancement methods such as microneedles help address this challenge. Earlier work in humans has demonstrated that the use of microneedles achieves plasma concentrations in the lower end of expected therapeutic values. Further flux enhancement is desired to …

Towards The Total Synthesis Of The Capuramycin Family Of Natural Products, Jesse M. Jacobsen

University of Kentucky Master's Theses

Despite over a century of advancement, tuberculosis remains a grave threat to world health. In particular, third world countries continue to struggle with the crushing weight of the disease. Furthermore, the emergence of drug resistance in TB strains poses a significant threat to the first world where incidence and mortality is low. The dwindling efficacy of current drug regimens necessitates research into new small molecules capable of arresting the growth and spread of TB. The capuramycin family of nucleoside antibiotics shows strong potential to become part of this new generation of anti-TB small molecules. Indeed, their ability to inhibit Translocase …

The Influence Of Antidiabetic Medications On The Development And Progression Of Prostate Cancer, Anna Elizabeth Hitron

University of Kentucky Master's Theses

The development of prostate tumors has been linked to co-morbid diabetes mellitus (DM) in several studies, potentially through the stimulation of insulin-like growth factor receptor (IGFR). This study evaluates the effect of anti-diabetic medication use on the development of high grade tumors and time to tumor progression compared to non-diabetics. This retrospective, nested case control study identified patients with prostate cancer (PCa) from the Kentucky Medicaid Database. Cases were diagnosed with PCa and DM and using at least one of the following antidiabetic medications; sulfonylureas, insulin, metformin or TZDs. Cases were further stratified on their insulin exposure resulting from therapy. …

Evaluation Of The Physicochemical Properties And Stability Of Solid Lipid Nanoparticles Designed For The Delivery Of Dexamethasone To Tumors, Melissa Howard

University of Kentucky Doctoral Dissertations

Pre-clinical and clinical trials suggest that pre-treatment with dexamethasone (Dex) may facilitate enhanced uptake of subsequently administered chemotherapeutic agents. To reduce the side effects associated with systemic administration of Dex, solid lipid nanoparticles (SLNs) containing dexamethasone palmitate (Dex-P) were prepared as a means of achieving tumor-targeted drug delivery. These studies were aimed at evaluating the physicochemical properties and both the physiological and storage stability of the SLNs.

SLNs were prepared using nanotemplate engineering technology. Stearyl alcohol (SA) was used as the lipid phase with Brij^® 78 and Polysorbate 60 as surfactants and PEG6000 monostearate as a long-chain PEGylating agent. …

Using Lean Principals To Improve Patient Flow, Keith Weinhold Mha, Fache, Eliot L. Friedman Md, Darlene Matthias Rn, Ms, Ocn, Mary R. Greenberg, Amy E. Levan Rn, Bsn, Ocn, Jill Korn Rn, Bsn, Ocn, Melissa Kratz Rn, Msn, Aocn, Mandy Melocheck Rn, Msn, Ocn, Cindy J. Fenton Rn, Ocn, Janine Barnaby Rph, Bcop, Jeanne Kenna Rn, Ocn, Jennifer Mesker Pharmad, Kyle Sabatino Rn, Msn, Aocn, Lori Turnbach, Maura Price Rn, Bsn, Ocn, Pamela Tobias Ms, Rhia, Patricia Shearburn Rn, Msn, Aocn, Ramona E. Chase Crnp, Stephanie Thomas, Pamela Repetz, Barbara Versage Rn, Mba, Cphq

Administration & Leadership

No abstract provided.