Pharmacy and Pharmaceutical Sciences Commons^™

Target Based Design And Synthesis Of Fused Pyrimidines In The Potential Treatment Of Cancer And Opportunistic Infection, Khushbu Shah

Electronic Theses and Dissertations

This dissertation describes an introduction, background and research progress in the areas of agents designed as (a) selective Pneumocystis jirovecii dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection; (b) inhibitors of microtubule polymerization and multiple receptor tyrosine kinase (RTK) for potential treatment of cancer; and (c) substrates for tumor-targeted therapy for cancer.

PCP is a host species-specific infection. Most of the drugs, synthesized and evaluated so far, have been tested against Pneumocystis carinii dihydrofolate reductase (the causative organism in rats), which would not necessarily be effective against pjDHFR (the causative organism in humans). Trimethoprim-sulfamethoxazole (TMP-SMX) combination, which has been …

Cyclodextrin As A Drug Carrier Increasing Drug Solubility, Malka Silberberg

The Science Journal of the Lander College of Arts and Sciences

The development of a new drug requires research and evaluation before the drug is approved to enter the market. One of the factors determining the efficacy of a drug is the aqueous solubility of the drug. A current problem in today’s pharmaceutical industry is the low aqueous solubility of many useful drugs. A drug with a low aqueous solubility will not readily be absorbed by the body. The low aqueous solubility of a drug is often due to the drug’s hydrophobic character. Drug enhancement methods are necessary to avoid the obstacle of drug insolubility and many methods have been developed. …

Development Of Emulsion-Based Adjuvants For Parenteral Influenza Vaccines, Sakalanunt Lamaisakul

Chulalongkorn University Theses and Dissertations (Chula ETD)

Generally, inactivated whole-cell and subunit vaccines are often less antigenic than live-attenuated vaccines, then they require the inclusion of adjuvants to improve immunostimulating activities. In the present study, microemulsion (ME) and nanoemulsion adjuvants were developed to evoke a safety and effective immune response of vaccine antigens. The emulsion systems including vegetable oil and nonionic surfactants have been formulated with or without cationic surfactant, cetyltrimethylammonium bromide (CTAB) and then sterilized by autoclaving. Physical properties, hemolytic activities and biological efficacies of all prepared emulsions were conducted. The results demonstrated that the autoclaving process caused a reduction in droplet size with narrow size …

The Big Patent Short: Hedge Fund Challenges To Pharmaceutical Patents And The Need For Financial Regulation, Ariel D. Multak

Fordham Journal of Corporate & Financial Law

The enactment of the America Invents Act (AIA) in 2011 ushered in a new system for post-grant patent review. In the interest of enhancing the efficiency of the patent regime by invalidating “bad” patents, certain requirements were relaxed. For example, the AIA created an examination process called inter partes review, which allows a party without legal standing to challenge the validity of a patent in front of the Patent Trial and Appeal Board. In the pharmaceutical patent context, it was expected that inter partes review would be utilized mostly by generic drug makers seeking to invalidate patents without incurring the …

Intravenous Solution Wastage In Hospital Pharmacy At Baptist Memorial Hospital-North Mississippi (Oxford), Yujing Zhang

Honors Theses

Introduction: IV solution wastage refers to IV medications made for a patient that remain unused by that patient for a variety of reasons, and have subsequently expired, or for other reasons cannot be used for another patient (recycled), and therefore must be disposed of. This problem is widespread across hospital pharmacies in the U.S. and the world. BMH-NM (Oxford) pharmacy utilizes many waste reduction strategies but has never monitored its IV solution wastage. Therefore, the objective of this study was to identify the number of IV solutions wasted in a month and the subsequent financial loss in terms of drug …

Effects Of Dioscin On Dna Methyltransferase 1 Protein Expression In Human Breast Cancer Cell Lines, David Andrew Means

Honors Theses

In previous experiments, the steroidal saponin, dioscin, which was extracted from the roots of the wild yam (Dioscorea villosa), was observed to have potent anti-proliferative effects on the human breast cancer cell lines MCF-7 and MDA-MB-231. Dioscin was also able to activate the transcription of tumor suppressor genes GATA3 and CDH1 in these cell lines. We hypothesize that the anti-proliferative effect of dioscin on human breast cancer cells could be mediated through the epigenome. Consequently, in order to explore this hypothesis, we have analyzed the expression of DNA methyltransferase 1 (DNMT1) protein in these cells. MCF-7 and MDA-MB-231 cells were …

Gastrointestinal Bleeding Events And Statin Use: A Large Propensity Score-Matched Retrospective Cohort Study, Ashley I. Martinez

Theses and Dissertations--Pharmacy

Literature is conflicting regarding the association between statin use and gastrointestinal (GI) bleeding. This study sought to determine whether there is an association between statin use and GI bleeding by comparing incidence of gastrointestinal events between statin users and an active comparator group.

Data was obtained from a large administrative claims database composed of subjects enrolled in a selection of insurance plans throughout the United States from 2009-2014. New statin users (exposed) and thyroid medication users (active comparator, unexposed) were followed from the baseline period (one year prior to medication initiation) until first event, discontinuation, or disenrollment. Subjects were matched …

The Development Of Bsn272 From Prevention Of Diet-Induced Hyperlipidemia In Mice To A Potential Therapy For Prader-Willi Syndrome In Humans, Jarrod B. Williams

Theses and Dissertations--Pharmacy

While type 2 diabetes mellitus (T2DM) is distinguished as a disorder of blood glucose homeostasis, the vast majority of patients afflicted with this disease in the US present with the entire complement of the metabolic syndrome: abdominal obesity, hypertriglyceridemia, low HDL levels, elevated blood pressure, and elevated fasting plasma glucose. Current guidelines aim to treat each of these disorders, but do so individually even though they are manifestations of common pathologies. In other words, a patient will be prescribed different medications for diabetes, blood pressure, CVD prevention, etc., while the only single treatment aimed at the myriad of disorders together …

Effects Of Core And Shell Modification To Tethered Nanoassemblies On Sirna Therapy, Steven Rheiner

Theses and Dissertations--Pharmacy

siRNA therapy is an emerging technique that reduces protein expression in cells by degrading their mRNAs via the RNA interference pathway (RNAi). Diseases such as cancer often proliferate due to increased protein expression and siRNA therapy offers a new method of treatment for those diseases. Although siRNA therapy has shown success in vitro, it often fails in vivo due to instability in the blood stream. To overcome this limitation, delivery vehicles are necessary for successful transfection of siRNA into target cells and cationic polymers have been widely studied for this purpose. However, complexes between siRNA and delivery vehicles made …

Development Of Diverse Size And Shape Rna Nanoparticles And Investigation Of Their Physicochemical Properties For Optimized Drug Delivery, Daniel L. Jasinski

Theses and Dissertations--Pharmacy

RNA nanotechnology is an emerging field that holds great promise for advancing drug delivery and materials science. Recently, RNA nanoparticles have seen increased use as an in vivo delivery system. RNA was once thought to have little potential for in vivo use due to biological and thermodynamic stability issues. However, these issues have been solved by: (1) Finding of a thermodynamically stable three-way junction (3WJ) motif; (2) Chemical modifications to RNA confer enzymatic stability in vivo; and (3) the finding that RNA nanoparticles exhibit low immunogenicity in vivo.

In vivo biodistribution and pharmacokinetics are affected by the physicochemical …

Halo- And Solvato-Fluorochromic Polymer Nanoassemblies For Cancer Theranostics, Derek Alexander Reichel

Theses and Dissertations--Pharmacy

Theranostics is an emerging treatment approach that combines diagnostics with therapy in order to personalize treatment regimens for individual patients and decrease cancer mortality. Previously, nanoparticles entrapping conventional fluorescent dyes were developed for cancer theranostics, but fluorescent nanoparticles did not allow clinicians to significantly improve cancer treatments.

The use of fluorescent dyes that are sensitive to solvent acidity (halo-fluorochromism) and polarity (solvato-fluorochromism) may overcome the limitations of fluorescent nanoparticles and improve cancer therapy by enabling researchers to detect chemical properties within the nanoparticle core environment. The model halo- and solvato-fluorochromic dye Nile blue was attached to the core of nanoscale …

Pneumococcal Conjugate Vaccine 13 Coverage In Children, High-Risk Adults 19-64 Years Of Age, And Adults Over 65 Years Of Age In A Commercially Insured U.S. Population, Joseph C. Vanghelof

Theses and Dissertations--Pharmacy

This thesis aimed to elucidate the demographic characteristics associated with elevated or reduced rates of pneumococcal conjugate 13 (PCV13) vaccination.

A retrospective cohort study was performed using the Truven Health MarketScan® Database. Three cohorts were created corresponding to populations for which the CDC recommends PCV13 vaccination. Cohort 1: children < 36 months of age. Cohort 2: adults 19-64 years of age with high infection risk. Cohort 3: adults > 65 years of age. Odds of having a PCV13 claim were calculated for each cohort.

For Cohort 1, 78% out of a total of 353,214 subjects had a sufficient number of PCV13 doses to meet CDC recommendations. For Cohort 2, 3.7% out of a total of 673,157 subjects had a PCV13 …

Rational Design, Synthesis, And Characterization Of Novel Mpges-1 Inhibitors As Next Generation Of Anti-Inflammatory Drugs, Ziyuan Zhou

Theses and Dissertations--Pharmacy

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are currently widely used as fever and pain relief in patients with arthritis and other inflammatory symptoms. NSAIDs effect by inhibiting cyclooxygenase-1 (COX-1) and/or cyclooxygenase-2 (COX-2). COX isozymes (COXs) are key enzymes in the biosynthesis of prostaglandin H₂ (PGH₂) from arachidonic acid (AA). It is now clear that prostaglandin E₂ (PGE₂), one of the downstream products of PGH₂, is the main mediator in both chronic and acute inflammation. Microsomal prostaglandin E synthase (mPGES-1) is the terminal enzyme of COX-2 in the PGE₂ biosynthesis pathway. …

Effects Of In Utero Nicotine Exposure On Immune Cell Disposition After P. Aeruginosa Lung Infection, Nayon Kang

Theses and Dissertations--Pharmacy

Current smoking cessation guidelines recommend nicotine replacement therapy (NRT) to assist pregnant smokers to quit, but this is without strong evidence for effectiveness and safety. Nicotine, the main addictive component of tobacco, is known to exert physiological effects by binding to its receptor, the nicotinic acetylcholine receptor (nAChR). Recent studies have identified the presence of nAChRs in non-neuronal cells, and in macrophages, functional alteration upon stimulation with nicotine has been documented.

To understand the impact of in utero nicotine exposure on various immune cell disposition and function, we designed preliminary studies using an in vivo model of P. aeruginosa infection. …

Gene Expression Profiles Reveal Alternative Targets Of Therapeutic Intervention For The Treatment Of Drug-Resistant Non-Small Cell Lung Cancers, Madeline J. Krentz Gober

Theses and Dissertations--Pharmacy

More than 80% of lung cancer patients die from drug-resistant, metastatic disease. Our focus is to identify new drug targets and alternative therapeutic strategies to improve outcomes for this majority of lung cancer patients. We aimed to satisfy the need for new treatment approaches by leveraging the information gained from the development of two multigene biomarker predictors of Epidermal Growth Factor Receptor Inhibitors (EGFRI) response in Non-Small Cell Lung Cancer (NSCLC). From these data, we first identified TGFβ signaling as a possible modulator of EGFRI resistance and I hypothesized that TGFβ signaling participates in the development and maintenance of erlotinib-resistance …

Insulin Actions On Hippocampal Neurons, Shaniya Maimaiti

Theses and Dissertations--Pharmacology and Nutritional Sciences

Aging is the main risk factor for cognitive decline. The hippocampus, a brain region critical for learning and memory formation, is especially vulnerable to normal and pathological age-related cognitive decline. Dysregulation of both insulin and intracellular Ca2+ signaling appear to coexist and their compromised actions may synergistically contribute to neuronal dysfunction with aging. This dissertation focused on the interaction between insulin, Ca2+ dysregulation, and cognition in hippocampal neurons by examining the contributions of insulin to Ca2+ signaling events that influence memory formation. I tested the hypothesis that insulin would increase cognition in aged animals by altering Ca2+-dependent physiological mechanisms involved …

A Pilot Stability Study Of Dehydroepiandrosterone Rapid-Dissolving Tablets Prepared By Extemporaneous Compounding, Steven D. Rush, Charlene Vernak, Fang Zhao

Pharmacy Faculty/Staff Publications

Dehydroepiandrosterone supplementation is used to treat a variety of conditions. Rapid-dissolving tablets are a relatively novel choice for compounded dehydroepiandrosterone dosage forms. While rapid-dissolving tablets offer ease of administration, there are uncertainties about the physical and chemical stability of the drug and dosage form during preparation and over long-term storage. This study was designed to evaluate the stability of dehydroepiandrosterone rapid-dissolving tablets just after preparation and over six months of storage. The Professional Compounding Centers of America rapid-dissolving tablet mold and base formula were used to prepare 10-mg strength dehydroepiandrosterone rapid-dissolving tablets. The formulation was heated at 100°C to 110°C …

Assessing Student Perceptions Of The Pharm.D. Degree At A Private Tertiary Medical University In India, Kobi T. Nathan, Kelly Conn, Christine R. Birnie

Pharmacy Faculty/Staff Publications

Background: Pharmacy education in India has expanded to include the Doctorate of Pharmacy degree (Pharm.D.). With clinical practice in early development, job opportunities in India are limited. Graduates often consider pharmacy opportunities abroad.

Aims: This study compares Indian students’ career aspirations related to the Pharm.D. degree before and after beginning their programmes.

Methods: A 5-point Likert scale paper survey with open ended questions was distributed to all Pharm.D. students (Year 1- 6) at a medical university in India.

Results: With a response rate of 83% (144/173), over half of the students’ primary goal was to pursue careers abroad post-graduation (54.2% …

Evidence For The Use Of ‘‘Medical Marijuana’’ In Psychiatric And Neurologic Disorders, Christopher Noel

Pharmacy Faculty/Staff Publications

Introduction: Cannabis is listed as a Schedule I substance under the Controlled Substances Act of 1970, meaning the US federal government defines it as an illegal drug that has high potential for abuse and no established medical use; however, half of the states in the nation have enacted “medical marijuana” (MM) laws. Clinicians must be aware of the evidence for and against the use of MM in their patients who may consider using this substance.

Methods: A PubMed database search was performed using the text string: “Cannabis”[Mesh] OR “Marijuana Abuse”[Mesh] OR “Medical Marijuana”[Mesh] OR “Marijuana Smoking”[Mesh] OR “cannabi*” OR “tetrahydrocannabinol.” …

An Evaluation Of The Impact Of Immediate Compared To Delayed Feedback On The Development Of Counselling Skills In Pharmacy Students, Alexander Delucenay, Kelly Conn, Anthony Corigliano

Pharmacy Faculty/Staff Publications

Background: Simulation-based counselling using standardised patients (SPs) provide pharmacy students an authentic approach to training; limited data exists regarding student performance using immediate feedback approaches.

Aims: To compare grades of students receiving immediate feedback verses (vs.) delayed feedback.

Methods: A pre-trial assessment of student perceptions and an unblinded randomised trial comparing immediate and delayed feedback. Third year pharmacy students (n=153) counselled SPs in four clinical “experiences”; student grades were the primary outcome. Student t-test and repeated measures were used to compare grades between groups and grades over time.

Results: During pre-trial surveys 50% of students preferred immediate feedback, 22% …