Other Pharmacy and Pharmaceutical Sciences Commons^™

Absolute Quantification And Identification Of Rna From Rna-Lipid Nanoparticles Using High Resolution Mass Spectrometry, Jason C. Funderburk

Theses and Dissertations

RNA therapeutics are a rising drug category with potential use for a range of conditions encompassing infectious diseases to therapies for cancer, diseases, and genetic disorders. RNA-lipid nanoparticles (RNA-LNPs) are the prominent delivery method for these therapeutics approved products include mRNA vaccines and polyneuropathy treatments. The emergency use authorizations and orphan drug status of current RNA-LNP drugs has allowed approval without finalization of the regulatory analytical procedures for quality monitoring. The objective of the study was to develop an LC-MS assay to simultaneously measure identity and concentration of two therapeutically relevant intact RNA constructs extracted from RNA-LNPs to enhance quality …

Immersive Medical Practice And Clinical Training: Virtual And Mixed Reality In Pharmacy And Orthopedic Surgery, Silas Semprini De Toledo Contaifer

Theses and Dissertations

Extended‑reality (XR) technologies including virtual reality (VR) and mixed reality (MR) offer new ways to improve training and surgical precision. This thesis evaluates their educational and clinical impact through two complementary studies.

Specific Aim 1 compared an immersive 360° video VR module with conventional training for teaching USP < 797> sterile‑compounding skills to second‑year PharmD students (N = 36). VR trainees raised their knowledge from 6.14 ± 1.55 to 8.69 ± 1.07, yet the overall post‑test advantage versus control was not statistically significant (U = 71.50, p = 0.21). Item‑level McNemar testing showed significant VR‑exclusive gains on three critical questions (K5, K6, …

On! Original Flavor Oral Nicotine Pouch Characterization: Biorelevant In Vitro Nicotine Release Apparatus Assessment, Jason C. Funderburk, Melissa Morgan, Maria Lasaosa Garcia, Andreas S. L. Mendez, Matthew S. Halquist

Graduate Research Posters

Background: Oral nicotine pouch (ONP) use is rising. The sales of ONPs in 2019 were 126 million units, increasing to 808 million units in 2022. Understanding ONP in vitro release is critical for assessing exposure to ONP products.

Methods: The commercial brand ON! ONPs with nicotine label claims of 2, 4, and 8 mg, were evaluated in vitro for cumulative nicotine release using the bidirectional transmucosal apparatus (BTA) for 90 minutes. Nicotine quantification was performed by HPLC-PDA. For pH determination, ONP samples were prepared in water or artificial saliva (pH 6.8) with measurements for 30 minutes. BTA results were compared …

Cardiometabolic Genomics And Pharmacogenomics In Filipino Americans: A Cross-Sectional Study, Khalifa Y. Alrajeh

Theses and Dissertations

Background: Heart disease remains a leading cause of death in the country, with significant ethnic disparities. Filipino Americans (FAs), the third-largest Asian subgroup in U.S., face an elevated burden of dyslipidemia, a primary modifiable risk factor for heart disease. Objectives: This community-based study addresses critical knowledge gaps by characterizing the cardiometabolic and genetic factors contributing to dyslipidemia among FAs and implications for personalized cardiovascular drug therapies, particularly statin pharmacogenomics (PGx). Methods: We characterized dyslipidemia prevalence in FAs and major ethnic subgroups using nationally representative NHANES data. We examined associations between uric acid (UA) levels and lipid profiles, …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

Development And Optimization Of A Low Volume Air-Jet Dry Powder Inhaler (Dpi) Platform For The Delivery Of High Dose Aerosolized Powder To Infants, Connor Howe

Theses and Dissertations

The goal of this research project was to develop an infant air-jet dry powder inhaler (DPI) platform for high-efficiency nose-to-lung (N2L) aerosol administration to infants through optimization of individual system components followed by expansion of the system to higher doses and different formulations using a new approach. Primary challenges associated with aerosol delivery to infants using the N2L route include the extremely narrow extrathoracic airways, short inspiratory times (~0.2 sec), low safe airway pressure (H₂O), and very low volumes of air (~10 mL) available to form the aerosol. The infant air-jet DPI system was comprised of three main …

Pharmacists' Role In Opioid Use Disorder And Overdose Prevention And Treatment And Their Attitudes And Perceptions Towards Distributing Naloxone Under A Standing Order, Stephen C. Ijioma

Theses and Dissertations

Background: Opioids are a class of drugs that bind to opioid receptors (mu, delta, and kappa), located in the central and peripheral nervous systems, to exert responses such as analgesia, respiratory depression, euphoria, and miosis. The opioid epidemic is characterized in large part by an increase in opioid overdose deaths. Community pharmacists are one of the most accessible healthcare professionals who frequently interact with patients and can implement OUD and opioid overdose prevention strategies. Treatment for opioid overdose and OUD include naloxone for overdose deaths as well as medication-assisted treatment for OUD.

Objective: The specific aims of this thesis include …

Development Of An Online Warfarin Dosing Platform Using R Programming Language To Facilitate Healthcare Professional Duties And Limit Medication Related Errors., Monther Alsultan

Graduate Research Posters

Development of an online warfarin dosing platform using R programming language to facilitate healthcare professional duties and limit medication related errors.

Monther Alsultan, Joshua M. Morriss, Daniel Contaifer Jr, Suad Alshammari; Silas Contaifer, Rachel W Flurie, Dayanjan S. Wijesinghe^#

Department of Pharmacotherapy and Outcome Sciences

Objective: 1) Gain experience in developing platform agnostic, fully operational and clinically relevant web applications for effective pharmacist led patient care. 2) Create a decision- support tool using open source software to facilitate evidence-based management therapy of warfarin in clinical settings where it is available for everyone to use at anytime and anywhere.

Introduction: …

Frequency Of Genetic Polymorphisms Of Cyp2c19 In Native Hawaiian, And Asian And Pacific Islander Subgroups: Implications For Personalized Medicine, Khalifa Y. Alrajeh, Youssef Roman Dr

Graduate Research Posters

Pharmacogenetic testing, where prescriptions are tailored to the individual patient based on his/her genetic makeup, increases the ability to predict individual drug response. However, little is known about the prevalence of clinically actionable pharmacogenes in diverse populations. This study seeks to assess the prevalence of select drug-gene alleles that are implicated in the metabolism of commonly prescribed drugs, so-called Very Important Pharmacogenes (VIPs). The results of this study will fill in the gaps of knowledge of VIPs in underrepresented populations and characterize their potential risk for drug adverse events or due to their underlying genetic polymorphisms, especially in patients of …

Development Of An Online Warfarin Dosing Platform Using R Programming Language To Facilitate Healthcare Professional Duties And Limit Medication Related Errors., Monther Alsultan

Graduate Research Posters

Development of an online warfarin dosing platform using R programming language to facilitate healthcare professional duties and limit medication related errors.

Monther Alsultan, Joshua M. Morriss, Daniel Contaifer Jr, Suad Alshammari; Silas Contaifer, Rachel W Flurie, Dayanjan S. Wijesinghe

Department of Pharmacotherapy and Outcome Sciences

Objective: 1) Gain experience in developing platform agnostic, fully operational and clinically relevant web applications for effective pharmacist led patient care. 2) Create a decision- support tool using open source software to facilitate evidence-based management therapy of warfarin in clinical settings where it is available for everyone to use at anytime and anywhere.

Introduction: Healthcare …

Reward-Related Effects Of Amphetamines Administered By Electronic Cigarette, Lucas Wohler

Theses and Dissertations

While e-cigarette vaporizers are primarily used for the delivery of nicotine, they can also be used to administer a wide range of other substances of abuse including stimulants such as d-amphetamine and methamphetamine. Methamphetamine and prescription amphetamines are widely abused throughout the United States and across the world leading us to believe there may be abuse potential with vaping methamphetamine as vaping becomes increasingly popular. In the present study, methamphetamine and amphetamine vapor were assessed using vapor capture methods. The vapor samples were then analyzed using liquid chromatography mass spectroscopy (LC-MS). Three experiments were carried out to examine the abuse …

Continuous Manufacturing Of Pharmaceuticals Using Novel Platforms, Sarah S. Aboelela

Theses and Dissertations

Pharmaceuticals have been synonymously manufactured in a centralized, batch mode with less attention to process and formulation understanding. However, due to rising drug costs, shortages, and robustness issues, in addition to the alarming lack of flexibility and agility, regulatory agencies have pushed towards switching to continuous processes. They believed in continuous manufacturing, providing cleaner, flexible, and more efficient processes. Hence, it was foreseen to reduce development and manufacturing costs, time, and environmental impact and ensured drug product quality. Over the last two decades, continuous manufacturing quality, environmental, and economic advantages have been evident through many case studies and approved products …

Health Outcomes And Utilization Associated With Renal Diseases In Patients With Cancer In The United States, Mitisha Dedhia

Theses and Dissertations

Background: Adverse events and impairments associated with cancer and its treatments causes worse outcomes. Increased incidence of renal diseases among cancer patients is of particular concern. Objective: To determine the risk factors for renal disease in cancer patients and compare healthcare costs, utilization and health-related quality of life (HRQoL) of cancer patients with a renal disease and cancer patients without renal diseases. Methods: Medical Expenditure Panel Survey files from 2009 – 2018 for cancer patients was used for this study. Multiple logistic regression, generalized linear model, Poisson regression and multiple linear regression for analyses after adjusting for demographic, socioeconomic and …

Epigenetic Regulation Of Drug Metabolizing Enzymes In Normal Aging, Mohamad M. Kronfol

Theses and Dissertations

Geriatric populations are at a higher risk for adverse drug reactions (ADRs). This may be partly due to changes in drug metabolism in old age, but the underlying mechanisms are poorly understood. Prior research in humans and mice has shown age-associated changes to the expression of several genes involved in drug metabolism. Furthermore, studies of human blood showed that epigenetic regulation of genes encoding drug metabolizing enzymes change with age. However, it is unknown if genes in the liver are similarly affected. Therefore, we hypothesize that genes encoding drug metabolizing enzymes may show differential epigenetic regulation in the liver with …

National And Local Antibiotic Prescribing Trends And Prescribing Appropriateness In Older Adults, Fawaz M. Alotaibi

Theses and Dissertations

Background: Antibiotic overuse/misuse has been documented in several reports to increase the risk of Clostridioides difficile (C.diff) infection and antibiotic resistance. The older adult population is more prone to use antibiotic medications than any other age group due to decreased immune function, use of urinary catheters, ventilation during hospitalization and other factors. Antibiotic resistance and C.diff are major public health problems. However, studies examining the trends of antibiotic use and the association between the antibiotic use and negative health outcomes among older adults in the outpatient and emergency department settings are limited.

Objectives: The main objectives of this …

Understanding Medication Self-Management Capacity Among Older Adults Living In Low-Income Housing Communities, Amal M. Badawoud

Theses and Dissertations

Understanding Medication Self-Management Capacity among Older Adults Living in Low-Income Housing Communities

ABSTRACT

Background: Medication self-management capacity (MMC) is an individual’s cognitive and functional ability to self-administer a medication regimen as prescribed. Poor MMC is an issue in older adults often resulting in negative health outcomes and loss of independence. Therefore, understanding low-income older adults’ capacity to manage their medications may help identify individuals who are at risk for developing medication mismanagement and guide future intervention strategies based on an individual need to promote safe medication use and healthy aging in place in the community.

Objectives: 1) To determine the …

Molecular Pharmacology Of Non-Phyto-Cannabinoid Approaches For Treatment Of Neuropathic Pain, Nadejda A. Blajkevich

Theses and Dissertations

Approximately twenty million people in United States have some form of peripheral neuropathy. It has been shown that the CB₂ cannabinoid receptor is upregulated when there is peripheral nerve injury and activating the CB₂ receptor produces anti-inflammatory effects that translate to a reduction in signs of “neuropathic pain” in animal models. Elevating endogenous cannabinoids by inhibiting degradative enzymes has also been used to reduce neuropathic pain signs in laboratory animal models of pain. We hypothesize that the molecular pharmacology of these two approaches can be leveraged to optimize CB₁/CB₂ activation to improve non-phyto-cannabinoid treatments for …

Modeling Pharmaceutical Inhibition Of Glucose-Stimulated Renin-Angiotensin System In Kidneys, Ashlee N. Ford Versypt, Minu R. Pilvankar, Hui Ling Yong

Biology and Medicine Through Mathematics Conference

No abstract provided.

Economic Burden Of Renal Cell Carcinoma (Rcc) And Treatment Patterns, Overall Survival And Healthcare Costs Among Older Metastatic Rcc Patients, Hrishikesh P. Kale

Theses and Dissertations

Background

Renal cell carcinoma (RCC) is the most common type of kidney cancer. Patients diagnosed with metastatic RCC (mRCC) have shorter overall survival compared to those diagnosed at earlier stages. Several targeted therapies, which cost from $7,000 - $16,000 per month have been approved since 2005 to treat mRCC. In addition, there is a growing interest in the use of cytoreductive nephrectomy (CN) with targeted therapies among mRCC patients. However, little is known regarding the economic burden of RCC and role of CN and prescribing patterns of targeted therapies among older mRCC patients.

Objectives

1) To assess the economic burden …

Housing Status, Patient Characteristics, And Ed Utilization Associated With Medication Prescribing At Ed Discharge Among Homeless And Nonhomeless Adults In Urban Hospitals In The United States, Lauren Cox

Theses and Dissertations

This cross-sectional study used a weighted sample of ED visits contained in the 2010-2015 years of the National Hospital Ambulatory Care Survey-Emergency Department (NHAMCS-ED) dataset. The purpose of this study was to: 1) identify differences in predisposing, enabling, and need characteristics, and ED use and medication prescribing characteristics between homeless and nonhomeless ED users; 2) assess the association between housing status and medication prescribing at ED discharge, and identify variables contributing to the disparity in medication prescribing between homeless and nonhomeless ED users; and 3) assess the predisposing, enabling, need, and ED use characteristics that predict medication prescribing at ED …

Elucidation Of Substrate Binding Interactions For Human Organic Cation Transporters 1 (Slc22a1) And 2 (Slc22a2) Using In Silico Homology Modeling In Conjunction With In Vitro Site-Directed Mutagenesis And Kinetic Analysis, Raymond E. Lai

Theses and Dissertations

The organic cation transporters (OCTs) play a critical role in the absorption, distribution and elimination of many drugs, hormones, herbal medicines, and environmental toxins. Given the broad substrate specificity of OCTs, they fall victim to the high susceptibility for contributing to harmful drug-drug interactions. Further defining how human (h)OCTs mechanistically bind to its broad array of substrates will provide significant insight to the understanding and prediction of drug-drug interactions in polypharmacy patients and the advancement of future rational drug design for therapeutics targeting OCTs. The goal of the current study was to elucidate the critical amino acid residues for transporter-substrate …

Effects Of Hiv-1 Tat And Drugs Of Abuse On Antiretroviral Penetration Inside Different Cns Cell Types, Sulay H. Patel

Theses and Dissertations

Human immunodeficiency (HIV) infection can result in neurocognitive deficits in about one-half of infected individuals. Despite excellent systemic effectiveness, restricted antiretroviral penetration across the blood-brain barrier (BBB) is a major limitation in fighting HIV infection within the central nervous system (CNS). Drug abuse exacerbates cognitive impairment and pathologic CNS changes in HIV-infected individuals. This work investigates the effects of the HIV-1 protein, Tat, and drugs of abuse on factors affecting drug penetration into the brain.

Firstly, an in vitro model of the blood-brain barrier was built to study effects of HIV-1 Tat and methamphetamine (Meth) on integrity and function of …

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …

Development And Validation Of A Semi-Physiological Pharmacokinetic (Pbpk) Model To Predict Systemic And Pulmonary Exposures After Intravenous, Oral Administration And Pulmonary Inhalation Of Selected Drugs, Budesonide, Tobramycin And Ciprofloxacin, In Humans, Bishoy Hanna

Theses and Dissertations

Using a semi-PBPK modeling/quantitative meta-analysis approach, this project investigated what factors affect pulmonary and systemic exposures of Budesonide (BUD), Tobramycin (TOB), and Ciprofloxacin (CIP) after inhalation:

Three structurally different pulmonary disposition models were developed for each drug, including pulmonary absorption (all three), excretion (TOB and CIP) and sequestration (TOB) in a peripheral and central lung compartment. Systemic disposition parameters were estimated using available human mean plasma (c_p(t)) and sputum (c_s(t)) concentration profiles after IV administration, and GI absorption parameters were estimated from these profiles after oral administration. Pulmonary disposition parameters were estimated from c_p(t) …

Study Of Molecular Interactions Of Glycosaminoglycans And Glycosaminoglycan Mimetics With Their Protein Targets, Daniel K. Afosah

Theses and Dissertations

Glycosaminoglycans (GAGs) are complex linear chain carbohydrate molecules found on virtually all animal cell surfaces. Owing to their negatively charged nature, GAGs interact with a number of different proteins. Thus, although they have great potential as therapeutic agents, their apparent promiscuous interactions increase their side effect risk. GAG mimetics, including GAG oligosaccharides and non-saccharide GAG mimetics (NSGMs) are viable approaches to address this. This work discusses sulfated benzofuran thrombin inhibitors with submaximal protease inhibition, sulfated diflavonoid inhibitors of plasmin and GAG oligosaccharides with selectivity for human neutrophil elastase (HNE).

Anticoagulants are very important for the treatment of thrombotic diseases. The …

A Biorelevant In Vitro Model To Characterize In Vivo Release Of Bone Morphogenetic Protein-2 (Rhbmp-2), Deblina Biswas

Theses and Dissertations

Biorelevant in vitro release/dissolution tests are designed to predict the in vivo behavior of a drug and are crucial in understanding its in vivo performance. Currently, there is no standardized compendial in vitro release testing methods or regulatory guidance’s for release/dissolution testing of implants due to their complex physiological locations.Furthermore, existing compendial methods do not capture the local release profile of ‘novel’ parenterals in physiological low fluid volume surrounding areas.

Long acting and in situ forming implants with orthobiologic proteins and peptides have increased over the past few decades due to a better understanding of genetic engineering. One of these …

Investigation Of Polymeric Composites For Controlled Drug Release, Hsi-Wei Yeh

Theses and Dissertations

The Electrospray (ES) technique is a promising particle generation method for drug delivery due to its capabilities of producing monodisperse PLGA composite particles with unique configurations and high drug encapsulation efficiency. In the dissertation work, the coaxial dual capillary ES was used to generate drug-loaded core-shell PLGA particles to study the effects of particle filling materials, drug loading locations and particle shell thicknesses on the resultant in vitro release behaviors of the hydrophilic and/ or hydrophobic model drugs. Through release profile characterization of drug-loaded PLGA particles (particle size: 400 nm and 1 μm), it was confirmed that the co-encapsulation of …

Lung Disposition Model-Based Analyses Of Clinical Pharmacokinetic Profiles For Inhaled Drugs, Anuja Raut

Theses and Dissertations

There has been a desire to accurately interpret the inhaled pharmacokinetic (PK) profiles of drugs in humans to aid successful inhaled drug and product developments. However, challenges are layered, as 1) the drug dose delivered to the lung (DTL) from inhalers is a portion of the formulated dose but rarely determined; 2) lung delivery and regional deposition differ, depending on drug, formulation and inhaler; 3) drugs are not only absorbed from the lung but may also be from the gastrointestinal (GI) tract; and 4) in addition to absorption into the systemic circulation, multiple non-absorptive processes also eliminate drugs from the …

Using Semiphysiologically-Based Pharmacokinetic (Semi-Pbpk) Modeling To Explore The Impact Of Differences Between The Intravenous (Iv) And Oral (Po) Route Of Administration On The Magnitude And Time Course Of Cyp3a-Mediated Metabolic Drug-Drug Interactions (Ddi) Using Midazolam (Mdz) As Prototypical Substrate And Fluconazole (Flz) And Erythromycin (Ery) As Prototypical Inhibitors, Mengyao Li

Theses and Dissertations

The purpose of the project was to investigate the impact of IV and PO routes difference for MDZ, a prototypical CYP3A substrate, and two CYP3A inhibitors (CYP3AI) -FLZ and ERY-, on the magnitude and time course of their inhibitory metabolic DDI.

Individual semi-PBPK models for MDZ, FLZ and ERY were developed and validated separately, using pharmacokinetic (PK) parameters from clinical/in-vitro studies and published physiological parameters. Subsequently, DDI sub-models between MDZ and CYP3AIs incorporated non-competitive and mechanism-based inhibition (MBI) for FLZ and ERY, respectively, on hepatic and gut wall (GW) CYP3A metabolism of MDZ, using available in-vitro/in-vivo information. Model-simulated MDZ …

Quantitative Analysis Of 5-Chloro-2-Methoxy-N-[2-(4-Sulfamoylphenyl)Ethyl]Benzamide (Glyburide Analogue, Ga) In Mouse Plasma And Whole Blood Using A Micro-Extraction And Liquid Chromatography-Tandem Mass Spectrometry, Ankit Zalavadia

Theses and Dissertations

Pharmacokinetic evaluation of 5-chloro-2-methoxy-N-[2-(4- sulfamoylphenyl)ethyl]benzamide in mouse plasma demanded for a suitable bioanalytical method. No reported bioanalytical method exists to-date that can quantify concentration of this compound in any biological matrix. The purpose of this study was 1) to develop and validate a new bioanalytical method using a micro-extraction and LC-MS/MS to quantify the target analyte in mouse plasma and 2) to partially validate the method in whole blood. A bioanalytical method was developed and validated in both matrices for a linear concentration range of 2-1000 ng/ml. For both matrices, the reverse predicted concentration of calibration standards (-8.95% to 12.16% …