Pharmacy and Pharmaceutical Sciences Commons^™

Synthetic Explorations Towards Phenyl Benzazepine-Inspired Scaffolds And Synthesis Of Minor Cannabinoid Derivatives, Vishwashiv Kumar Emogaje

Theses and Dissertations

D1R is a compelling therapeutic target for correcting dopaminergic imbalances. However, existing ligands exhibit suboptimal pharmacokinetic properties. As such, we synthetically explored untouched structural modifications to the phenyl benzazepine scaffold. Cannabinoid-based molecules also display potential to treat neurological maladies and cancer. We synthesized Cannabichromene derivatives and uncovered enhanced anticancer activities.

Self-Medication And Pharmaceutical Dispensing In Egypt: Practices, Policies, And Regulatory Challenges, Lobna Fawzy Ali Shaheen

Theses and Dissertations

Access to safe and appropriate medications is a critical component of public health, particularly in low- and middle-income countries. In Egypt, self-medication and informal pharmaceutical dispensing have become deeply embedded practices shaped by systemic, economic, and cultural factors. This research explores the complex interplay between self-medication behaviors, pharmaceutical regulation, and healthcare access in Egypt. Through qualitative interviews with policymakers, pharmacists, physicians, industry professionals, and citizens, the research uncovers widespread informal dispensing of prescription-only medicines, driven by high out-of-pocket costs, limited insurance coverage, and high public reliance on pharmacists as primary care providers. Despite the presence of regulatory frameworks, weak enforcement, …

Targeting The Cd47/Calreticulin Axis In Triple Negative Breast Cancer Using Ha Grafted Chitosan Nanoparticles Loaded With Doxorubicin And Polygodial, Hadir M. Emara

Theses and Dissertations

Background: Triple-negative breast cancer (TNBC) is considered the most aggressive subtype of breast cancer. Although progress in cancer treatment has led to better results for different types of breast cancer, TNBC remains particularly challenging due to persistent resistance to both chemotherapy and immunotherapy. This resistance ultimately renders chemotherapy less effective and is frequently associated with substantial side effects. Immunosurveillance significantly impacts the onset of cancer, the rise of resistance to therapies, and the likelihood of tumor recurrence. In this immunomodulatory process, Cluster of Differentiation 47 (CD47) and Calreticulin (CALR) are two key regulators. CD47 expression is strongly linked to anti-phagocytic …

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 …

Local Lung Delivery Of Ginkgetin For Therapeutic Intervention In Lung Fibrosis, Cimone L. Richardson

Theses and Dissertations

Lung fibrosis (LF) is a progressive, irreversible pathological condition in the lungs that is ultimately fatal. Current drug treatments (nintedanib, pirfenidone, and nerandomilast) slow disease progression but cause significant systemic adverse effects due to oral administration. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, may play a role in LF progression and represent a novel anti-LF target. Ginkgetin (GKT), a natural biflavonoid, is a potent TRPV4 inhibitor with anti-inflammatory and antioxidative properties. Local lung delivery could achieve high local lung concentrations while minimizing systemic exposure. Accordingly, this project evaluates GKT's therapeutic intervention efficacy in LF via local lung …

Development Of A Strategy To Neutralize Ccl8 Activity And Ablate Ccl8 Cellular Targets, Bernardo Chavez

Theses and Dissertations

The chemokine CCL8 (monocyte chemoattractant protein-2) is a versatile signaling molecule involved in tumor progression, immune cell recruitment, and therapeutic resistance. Through activation of receptors including CCR1, CCR2B, and CCR5, CCL8 promotes leukocyte trafficking, epithelial–mesenchymal transition, and the establishment of immunosuppressive tumor microenvironments. In breast cancer and inflammatory diseases, elevated CCL8 levels correlate with poor clinical outcomes, making it a promising therapeutic target.

A strategy was developed to block CCL8 activity and selectively ablate CCL8 receptor expressing cells. A neutralizing monoclonal antibody, 1G3E5, was identified from a panel of murine candidates based on high affinity CCL8 binding. Sequencing revealed two …

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, …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

Discovering Therapeutic Strategies In Colorectal Cancer Via Synthetic Lethal Genetic Screens On Patient-Derived Organoid Models, Sana Khalili

Theses and Dissertations

Precision medicine is a revolutionary approach of targeting genetic alterations that are present only in tumor cells to find vulnerabilities that can be targeted with therapy. Identifying genetic dependencies in human colon cancer could help identify effective treatment strategies. Genome-wide CRISPR-Cas9 dropout screens can reveal all genetic dependencies, some of which could be exploited as therapeutic targets using existing drugs.

In this dissertation, I comprehensively characterized genetic dependencies present in a colon cancer organoid avatar, and validated tumor-specific selectivity of select pharmacologic agents. I identified all somatic mutations, all expressed genes, and conducted a genome-wide CRISPR dropout screen to elucidate …

Integrating Data-Driven And Mechanism-Driven Modeling In Drug Discovery And Hepatotoxicity Evaluation, Xuelian Jia

Theses and Dissertations

The pharmacological activities and hepatotoxicity significantly influence the success or failure of new drugs during drug discovery and development. Traditional experimental methods, such as animal models, are costly and time-consuming for chemical testing. There is a great need to develop in vitro and computational modeling to help identify the pharmacological activities and hepatotoxicity potential in the early stage of drug discovery and safety evaluation. In this dissertation, new computational models and associated modeling frameworks were described for predicting the biological profile and hepatotoxicity of chemicals. Firstly, a novel data mining and Quantitative Structure-Activity Relationship (QSAR) workflow was developed to construct …

Antioxidant And Anti-Inflammatory Potential Of Engineered Ceria Nanoparticles In The Management Of Alzheimer's Disease, Shanshan Shi

Theses and Dissertations

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that affects millions worldwide. Unfortunately, there are currently no effective therapies available to prevent or cure the disease. While current therapies aim to change AD progression, there is a growing need for novel therapeutic strategies that can effectively penetrate the blood-brain barrier (BBB) to target the underlying pathology of the disease. The BBB is a highly selective semipermeable barrier that separates circulating blood from the brain. It plays a crucial role in amyloid-β (Aβ) homeostasis and clearance dynamics, as Aβ accumulation is a key factor in the pathogenesis of AD. Aβ aggregation …

Improving Drug Repurposing Success: Integrating Large Database Claims Analysis In Drug Discovery, Joseph Magagnoli

Theses and Dissertations

Drug repurposing has emerged as an innovative strategy to identify new therapeutic uses for existing medications. However, with few notable exceptions, repurposing existing drugs has limited overall success, often failing in randomized controlled trials (RCTs) due to inadequate treatment efficacy in new clinical settings. To improve success rates, I propose a framework titled REMIDY: Retrospective and Experimental Methods Integration for Drug DiscoverY. The REMIDY framework incorporates retrospective claims analysis into the drug discovery process. I demonstrate that retrospective analysis can leverage extensive administrative and clinical data to address translational gaps between pre-clinical experimental models and RCTs. For example, pre-clinical experimental …

Medication Adherence Between Long-Acting Injectable And Oral Antipsychotic Medications In South Carolina Medicaid Beneficiaries With Schizophrenia, Pujing Zhao

Theses and Dissertations

Background: Schizophrenia is a chronic and serious mental disorder that affects millions of individuals worldwide. A recent study shows the prevalence of schizophrenia globally is about 1%. The primary schizophrenia treatment goal is to effectively manage symptoms and prevent relapses. Antipsychotic medications are very important for the treatment of schizophrenia. However, the prevalence of nonadherence to antipsychotic medication is high, with mean rates reaching 41.2%. In the realm of schizophrenia treatment, two primary categories of medications are utilized: long-acting injectable antipsychotics (LAI) and oral antipsychotic agents (OAP).LAI are administered at intervals spanning from two weeks to several months and have …

Evaluation Of Mechanism Of Action And Toxicity Of Novel Psychoactive Substances (Nps) Identified As Cannabinomimetics, Robert Michael Sears

Theses and Dissertations

Synthetic cannabinoid receptor agonists (SCRA), also referred to as synthetic cannabinoids (SCs), pose a significant public health risk, create an undue burden on local emergency departments, and present significant challenges for law enforcement officers and forensic laboratories. SCs are a diverse group of compounds sold with the intent to illicit psychoactive responses like tetrahydrocannabinol (THC), the primary psychoactive component in marijuana. Since their initial detection in 2004, illicit use of SCs has grown in popularity. Recognizing the dangers of SC use, the Drug Enforcement Agency has moved to schedule the analytes routinely identified in street drugs. Despite these efforts, the …

Chemotherapy Drug Release From Hollow Core Polyethyleneimine Nanoparticles, Brian Boyle

Theses and Dissertations

Novel anticancer delivery vehicles are arising from engineered nanostructured materials. This work involved the synthesis, characterization, and release of novel hollow core polymeric nanoparticles (HCPNPs) for controlled drug delivery. Polyethyleneimine (PEI) was bound to AuNPs, forming polymer-shell nanoparticles with dissolution of the gold core via iodine forming HCPNPs with drug intercalated DNA bound to the surface. A high density (85 molecules/particle) of DNA intercalated with daunorubicin was conjugated. Particles were spherical with an average diameter of 105.7 ± 17.3 nm and zeta potential of 20.4 ± 3.54 mV. We hypothesize the DNA backbone electrostatically condensed to the primary amines on …

Potent And Selective Small Molecule Mcl-1 Inhibitor Demonstrates Anti-Myeloma Activity And Overcomes Chemotherapy Resistance, Omar Sami Faleh Al-Odat

Theses and Dissertations

Despite a record number of clinical studies investigating various anti-myeloma treatments, the 5-year survival rate for multiple myeloma (MM) patients in the US is only 55%, and nearly all patients relapse. Poor patient outcomes demonstrate that myeloma cells are "born to survive” which means they can adapt and evolve following treatment. Thus, new therapeutic approaches to combat survival mechanisms and target treatment resistance are required. Importantly, Mcl-1, anti-apoptotic protein, is required for the development of MM and treatment resistance. This study looks at the possibility of KS18, a selective Mcl-1 inhibitor, to treat MM and overcome resistance. Our investigation demonstrates …

Integrated Computational Approaches: Elucidating Molecular Mechanisms Of Pathogenic Proteins And Designing Novel Inhibitors Against Mycobacterium Tuberculosis And Sars-Cov-2, Justin David Carbone

Theses and Dissertations

Chapter 1 introduces computational strategies in computer aided drug design (CADD), focusing on physics-based methodologies to enhance drug discovery. This chapter also discusses the theoretical foundations and practical applications of molecular dynamics (MD) simulations including free energy and stochastic kinetic analysis. In Chapter 2, CADD methods lead to development of inhibitors targeting the RNA Dependent RNA Polymerase (RdRP) of SARS-CoV-2. Inspired by the nucleotide inhibitor Molnupiravir, we aim to design a combinatorial library of 72 novel inhibitors capable of impeding a dual threat inhibition mechanism inducing lethal mutations along with stalling viral replication with specific selectivity to RdRp over Human …

To Decipher Genomic Evolution Of Dengue Virus And To Probe The Activation Mechanism Of A Her2 Directed Chimeric Antigen Receptor Toward Computer Aided Drug Design (Cadd), Mariya Hryb

Theses and Dissertations

This study encompasses three significant chapters focusing on diverse yet interconnected aspects of pharmaceutical research. Chapter 1 delves into the complexities of drug development, emphasizing the challenges and the pressing need for advanced technologies to streamline the process. Computational methods like Computer-Aided Drug Design (CADD) extend their scope beyond small molecules, aiding in the design of intricate biomolecules vital for biomedical advancements, especially in immunotherapy. Chapter 2 introduces the Near-Neutral Balanced Selectionist Theory (NNBST) validated through analysis of Dengue virus evolution. The unique features observed align with NNBST, surpassing existing theories. This approach offers a deeper understanding of viral evolution …

Tunable Dual-Phase Dual-Drug Delivery System Using A Plga Microparticle/Pva Hydrogel Composite, Timothy John Eck

Theses and Dissertations

Current drug-eluting coatings have demonstrated controlled long-term, sustained release but have only tried to mitigate short-term burst release as a negative side effect. For applications like wound healing, there is a need for a drug-eluting coating which is adjustable in both short- and long-term release, independent of each other. We present a tunable dual-phase dual-drug delivery coating composed of drug-loaded polymer microparticles and drug-loaded hydrogel which can control short term and long term release individually in this study. This coating was created using lidocaine and dexamethasone encapsulated in poly(D,L-lactide-co-glycolide) particles combined with lidocaine- and dexamethasone-loaded poly(vinyl alcohol) hydrogel. Hydrogel drug …

Behavioral Effects Of Novel Treatments For Pain Using Different Pathways, Danya M I Aldaghma

Theses and Dissertations

Pain is defined as an unpleasant sensation that is mostly caused by a stimulus from our surroundings. This sensation has the potential to become a significant concern, disrupting daily activities, and diminishing overall quality of life. However, it could also hold significant importance as it serves as a protective mechanism. Pain acts as an alarm system for the human body, alerting it to potentially harmful situations where tissues may be at risk of damage1. Despite the considerable advancements in pain treatment and the extensive knowledge scientists possess regarding the pathophysiology and pathways of pain, numerous medications aimed at alleviating pain …

Synthesis Of Leishmania Spp Antigens For The Development Of Vaccine Candidates, Dipesh Budhathoki

Theses and Dissertations

Leishmaniasis is a neglected tropical disease caused by the protozoan parasite of the genus Leishmania. Presently no vaccine against Leishmaniasis is available, so there is a need for new anti-leishmanial treatments, including an effective preventive vaccine. We focus on developing vaccine candidates based on leishmania’s cell surface carbohydrate antigens. Saccharides heavily envelop the cell surface of Leishmania, lipophosphoglycan (LPG) becoming a significant glycan in most leishmania species. Its intrinsic antigenicity makes this polysaccharide a useful target for developing conjugated vaccine candidates against all leishmaniasis variants. In this report, we present our progress towards the synthesis of the fragments of LPG …

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, …

Role Of Edaravone Nanosuspension In Preterm Labor And Birth Outcomes, Sruthi Sarvepalli

Theses and Dissertations

Annually, preterm birth (PTB) affects fifteen million infants, posing a significant risk of infant mortality and lifelong disability. Among various triggers, it is well-established that infection-associated oxidative stress and inflammation can induce preterm labor. There is no FDA approved medication for the prevention of PTB except tocolytics which provide marginal benefit at a later stage. Scarcity of therapeutic intervention and unmet medical need propelled us in investigating a novel drug molecule. Our current research is focused on investigating the potential of Edaravone (EDA), an FDA-approved antioxidant and anti-inflammatory medication, in delaying preterm labor and improving neonatal outcomes. Our goal is …

Addressing Inappropriate Polypharmacy: Investigating Perceived Facilitators And Barriers To U.S. Pharmacists' Ability To Recommend Deprescribing, Susanne Steiner

Theses and Dissertations

While the concurrent use of multiple prescriptions (polypharmacy) is common for those with chronic conditions, professional ownership is lacking when it comes to tapering or discontinuing potentially inappropriate medications. Our growing elderly population is especially vulnerable to negative risks associated with polypharmacy. Pharmacists are highly educated and skilled healthcare professionals working as critical touchpoints with patients; yet they are not empowered to deprescribe potentially inappropriate medications directly. This qualitative research study examined the perceived barriers and facilitators pharmacists encounter when pursuing deprescribing recommendations and initiatives with prescribers, healthcare staff, patients, and caregivers. Findings from this study revealed three key implications …

Drugging The Histone Acetyltransferase Ep300 Modulates Alternative Splicing At Schizophrenia Risk Genes, Shravani Malay

Theses and Dissertations

Purpose. We will evaluate the effects of drugging the epigenetic histone acetyltransferase (HAT) enzyme p300, encoded by the schizophrenia risk gene EP300, on genome-wide gene expression in neural cells. We hypothesize that drugging p300 will affect gene expression and alternative splicing of other schizophrenia risk genes. Our motivation is to identify potential new epigenetic treatment avenues for schizophrenia.

Methods. Prior to my joining the lab, an experiment was conducted using the novel p300 HAT inhibitor, A-485, to modulate genomic regulation in a neural cell line (SH-SY5Y). SH-SY5Y cells were exposed to 10μM of A-485 or vehicle (DMSO) for 24 …

Exploration Of Dopaminergic And Serotonergic Pathways Utilizing Pleiotropic Agents, Charles B. Jones Iii

Theses and Dissertations

2-(Benzoyl)piperidines (BPs) are at a crossroads of therapy and abuse. These compounds are a hybrid between the ADHD medication methylphenidate and abused stimulant cathinones. Here we use computational molecular modeling, synthesis, mutagenesis, and epifluorescence microscopy to further improve the understanding of and potential treatments for several neuropsychiatric disorders. Utilizing the BP scaffold and controlling chirality and aryl substitution, these agents were examined at DAT and SERT. From these investigations it has now been established that R isomer BPs are favored for DAT while S isomer BPs are favored for SERT. Aryl-substitution can greatly affect the selectivity of these agents with …

Nanoformulations Of Essential Oils Extracted From Pistacia Lentiscus And Boswellia Sacra And Investigation Of Their Anticancer, Antimicrobial, And Antioxidant Activities., Obaydah Abd Alkader Alabrahim

Theses and Dissertations

Essential oils (EOs) obtained from natural sources have shown promising biological and therapeutical properties such as anticancer, antimicrobial, and antioxidant activities, attributing to their high content of a variety of bioactive components. However, EOs’ therapeutic properties are limited by their low stability, poor bioavailability, high volatility, and low targeting ability. Therefore, the encapsulation and nanoformulation of EOs can maximize their therapeutical efficiency and physicochemical properties while overcoming their undesirable side effects and drawbacks. EOs extracted from the resins of Pistacia Lentiscus var. Chia (P.oil) and Boswellia Sacra (B.oil) are two promising EOs that have shown great therapeutic potential. P.oil was …

Drug Repurposing: New Mechanisms And Applications Of Existing Compounds, Biyun Celia Cui

Theses and Dissertations

HIV infection remains a significant global health challenge. Despite the widespread use of combination antiretroviral therapy, people living with HIV (PLWH) still face a disproportionate burden of major health problems. One of these problems is HIV-associated neurocognitive disorders (HAND), which includes a spectrum of cognitive, motor, and behavioral impairments. Although severe forms of HAND have decreased, milder forms are on the rise, posing a significant obstacle for PLWH.

The persistence of HIV in the central nervous system (CNS) is a challenge of HAND treatment and involves a combination of factors, including neurotoxic HIV proteins, chronic neuroinflammation, and comorbidity with substance …

Cdk8 And Cdk19 Mediator Kinases As Novel Targets In Advanced Prostate Cancer, Jing Li

Theses and Dissertations

Following androgen deprivation therapy (ADT), prostate cancers (PCa) progress to castration resistant prostate cancer (CRPC) status, where their growth becomes independent of androgen signaling, through altered androgen receptor (AR) signaling or other genetic or transcriptional changes. Metastatic CRPC remains incurable, and the most potent new drugs prolong survival by only a few months. There is an urgent need for novel agents against advanced CRPC. Here we have investigated the roles of CDK8 and CDK19, two isoforms of Mediator kinase, which regulates transcriptional reprogramming, in regard to their biological activities and as potential novel targets for the treatment of CRPC.

To …

Prevalence, Disparities, And Health Outcomes In Patients With Alzheimer’S Disease, Dementia, And Mild Cognitive Impairment, Xiaomo Xiong

Theses and Dissertations

Background: Alzheimer’s disease and related dementias (ADRD), an umbrella term to describe progressive neurodegenerative disorders linked to cognitive impairment and dementia, impose significant disease and economic burdens on the patients. Therefore, understanding the prevalence of these disorders is crucial, particularly for mild cognitive impairment (MCI), an intermediate phase between normal aging and dementia that may be reversible through early detection and intervention. Moreover, it is essential to identify the predictors of MCI to facilitate early detection. Additionally, addressing the existing health disparities in the prevalence and treatment of ADRD and MCI is imperative to help improve patients’ health outcomes. Meanwhile, …