Medicinal Chemistry and Pharmaceutics Commons^™

Elucidation Of Micro/Nanoplastic Signature Of Human And Murine Lung Tissue Utilizing Pyrolysis-Gas Chromatography/Mass Spectrometry, Aerlin D. Decker

Pharmaceutical Sciences ETDs

Micro-and Nanoplastics (MNPs) are ubiquitous biological pollutants that have been identified throughout a variety of biological samples. MNPs have been detected in several human tissues, such as the brain, kidneys, and liver. Lung tissue remains understudied for MNP accumulation despite the large surface area and clear path for exposure. Using Pyrolysis-Gas Chromatography Mass Spectrometry (Py-GC/MS), human lung tissue was evaluated for 12 different polymers, enabling quantification of total plastic per gram of tissue to be identified. Further analysis was performed with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) to investigate heavy metal accumulation in human lung samples and determine whether a …

Quantitative Determination Of Nano Delivered Kras Sirna, Axel S. Deraspe

USF Tampa Graduate Theses and Dissertations

This study focuses on the development and validation of analytical methods for the detection of therapeutic KRAS-targeting siRNA in biological systems. Physicochemical characterization showed that p5RHH-formulated siRNA nanoparticles exhibit a controlled nanoscale size distribution, moderate polydispersity, and a negative zeta potential, suggesting colloidal stability and potential suitability for cellular uptake. Scanning electron microscopy confirmed a predominantly spherical morphology with a relatively uniform size distribution, consistent with dynamic light scattering measurements.

To enable accurate siRNA quantification, stem–loop reverse transcription (SL-RT) coupled with SYBR Green–based quantitative Polymerase Chain Reaction (qPCR) was optimized. Key parameters, including a primer concentration of 100 nM and …

Dual-Modal Tumor Imaging Using Functionalized Iron-Oxide Nanoparticles For Mri And Fluorescence, Kevin Secades

USF Tampa Graduate Theses and Dissertations

Accurate tumor imaging is essential for early cancer detection and treatment monitoring [1]. Technetium-99m (Tc-99m) is a commonly used radioisotope for medical imaging, but its reliance on gamma-ray emission poses challenges related to safety, accessibility, and regulatory constraints[2-5]. This research proposes the development of a dual-modal imaging approach by functionalizing iron-oxide nanoparticles (IONPs) with the fluorescent chromophore Cy5, enabling both MRI contrast enhancement and optical imaging for improved tumor specificity. IONPs provide strong T2-weighted MRI contrast [6], while conjugated near-infrared (NIR) chromophores allow for high-resolution fluorescence imaging [7], making this proposed system adaptable for both in vitro and in vivo …

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 …

Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner

Honors Undergraduate Theses

Background: Patients with cancer often experience symptoms related to disease, complications, and treatment. One potential method of alleviating these symptoms is traditional Chinese herbal medications (TCHM). This rapid review explores the role of traditional Chinese herbal medications in treating cancer-related symptoms in older adults.

Purpose: The purpose of this rapid review is to gain and provide a better understanding of the effects of TCHM on cancer-symptom management in the older adult population. This review explores the association between TCHM and effects on cancer symptoms in older adults, including interactions, toxicity, and signs/symptoms of TCHM use that may be useful information …

Marigold-Silver Nanoparticles (Agnps) Complex: Characterization, Therapeutic Potential, And Future Approaches For Lung Injury Via Antioxidant And Anti-Inflammatory Effects, Navdeep Kaur

USF Tampa Graduate Theses and Dissertations

Chronic respiratory diseases (CRDs) and other lung conditions are a key cause of the problems facing global health, as they greatly increase morbidity, death, and the financial burden. In order to achieve the third Sustainable Development Goal of the United Nations, which is to reduce premature mortality from non-communicable illnesses by one-third by 2030, updated epidemiological statistics are crucial for directing prevention, control, and treatment measures. One of the major reasons of illness and death globally is chronic obstructive pulmonary disease (COPD). Lung damage and the emergence of CRDs, such as asthma, emphysema, COPD, and other respiratory disorders, are largely …

Formulation And Characterization Of Albumin Nanoparticles For Nsclc Photochemotherapy, Faisal Mohammad Shamim Khan

USF Tampa Graduate Theses and Dissertations

Non-small Cell Lung Cancer (NSCLC) is the most common type of lung cancer and is a leading cause of worldwide cancer-related death, which is a strong motivation to develop more efficacious approaches to its treatment. This thesis outlines the construction of folate-targeted bovine serum albumin (FA-BSA) nanoparticles co-loading Chlorin e6 (Ce6), a photodynamic therapy photosensitizer, and Evofosfamide (EVO), a hypoxia-activated prodrug, to enable synergistic photochemotherapy. The 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) is a water-soluble carbodiimide coupling reagent and used for amide bonds between carboxylic acid and amines. FA-BSA nanoparticles were prepared through a desolvation approach and stabilized through crosslinking by the carbodiimide reagent …

Comparative Expression Of Cgmp-Dependent Protein Kinase G (Pkg) From Plasmodium And Toxoplasma, Tsopmo Asaah

Theses, Dissertations and Culminating Projects

Malaria and Toxoplasmosis are life threatening diseases to humans. The search for a cure and control of these diseases is still one of the major challenges of scientists worldwide. In this research we focused on two Malaria species; Plasmodium bergei² (Pb) and Plasmodium falciparum¹ (Pf) and also on Toxoplasma gondii. Part of the life cycle of these organisms is regulated by the enzyme cyclic GMP-dependent protein kinase G (PKG)⁴. This is our drug target in this research. We believe that inhibiting this enzyme will be a great step in fighting these diseases. In this research, we devised a comparative study …

Utilization Of Bixin-Loaded Polycaprolactone Nanoparticles To Ameliorate E-Cigarette-Induced Damage To Human Bronchial Epithelial Cells, Sophia R. Claymore

USF Tampa Graduate Theses and Dissertations

Electronic cigarettes (e-cigs) have increased in popularity and usage over the last few decades. E-cigs are generally composed of a liquid containing nicotine flavoring chemicals, a battery, a vaporization chamber, and a coil that heats the liquid upon inhalation of the mouthpiece. E-cigs were initially introduced as a healthy alternative to cigarette smoking. However, recent research has demonstrated that e-cigs elicit comparable cytotoxic and dangerous effects to conventional cigarettes. Bixin has been introduced in recent research as a candidate for therapeutic applications due to its innate anticancer, antioxidative, and anti-inflammatory characteristics. Nanoparticles (NPs) have emerged over the past few decades …

Evaluating The Protective Role Of Epo-R76e In Oxidative Stress-Induced Cell Death In Retinal Pigment Epithelium, Jemima Alam

USF Tampa Graduate Theses and Dissertations

Age-Related Macular Degeneration (AMD) causes dysfunction and loss of Retinal pigment epithelium (RPE). The degeneration and death of RPE cells causes irreversible visual impairment. Oxidative stress is a widely accepted triggering factor for RPE dysfunction. A hormone called Erythropoietin (EPO) is responsible to facilitate the erythropoiesis process, prevents progenitor cells from apoptosis and protects photoreceptors downregulating retinal degeneration. In this study, we aim to elucidate the role of EPO in downregulating oxidative stress in RPE. It is hypothesized that EPO will have a positive impact on suppressing oxidative stress and ferroptosis-mediated RPE degeneration due to its vital role in apoptosis …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

Synergetic Effect Of Cellulose And Chitosan Polymers In Cancer Treatment, Grace Peterson

Graduate Theses, Dissertations, and Problem Reports (ETD)

This research explores the development of a biocompatible, natural drug delivery system designed for targeted cancer therapy. Lung cancer cells are used in these particular tests, but further research indicates treatment could be used for various cancer types. Traditional cancer treatments like chemotherapy are often limited by poor selectivity for tumor cells, causing significant damage to healthy tissues. The study proposes a dual-layered delivery system, utilizing Carboxymethyl Cellulose (CMC) as the core material and a charge-reversible chitosan shell to encapsulate and target cancer drugs. CMC, with its water solubility and ability to form stable gels, serves as a stable drug …

Identification Of Fentanyl And Fentanyl Analogs Found In Human Urine Using Gas Chromatography-Mass Spectrometry, Adam M. Fisher

Electronic Theses & Dissertations (2024 - present)

Identification of fentanyl and its analogs in unknown samples is a frequent practice completed in forensic crime labs, as the fentanyl epidemic continues. With the continued increase in illicit drug use, crime labs are not able to keep up with the flooding of new fentanyl analogs being developed, resulting in new analogs slipping past the crime labs’ authority. This research is to start to develop a database of commonly found fentanyl analogs in New York State. Gas Chromatography-Mass Spectrometry (GC-MS) is a widely used method for the detection and identification of illicit drugs in forensic crime labs. A database that …

Impact Of Tetrahydrocannabinol (Thc) On Daphnia Magna Heart Rate, Ashley Cosgrave

Williams Honors College, Honors Research Projects

Marijuana (Cannabis) is currently federally illegal within the United States and classified as a Schedule I drug. This leaves a large research gap on the impacts of Tetrahydrocannabinol (THC) use. Daphnia magna are frequently used as a model organism for the human heart and toxicology screenings due to their myogenic heart, similarities in physiological pathways, and sensitivity to toxins. As such, in order to bridge the research gap and uncover potential use of Daphnia magna as a model organism for humans in regard to impact on heart rate, we hypothesized that if Daphnia magna possess CB1 receptors or an equivalent …

Reversible Degradation Of Peptidoglycan By Lytic Transglycosylases, Aaron Devereaux

Theses and Dissertations (Comprehensive)

Antimicrobial resistance continues to be a burden on the global healthcare system with an estimated cost of billions of dollars and millions of deaths each year. Recently, there has been little to no development on new antibiotics to treat bacterial infection, and any that are developed become resisted to within a few years. Both Gram-positive and Gram-negative bacteria contain a mesh-like layer called peptidoglycan (PG) that surrounds their cells providing strength, cell shape, and protection from their environments. This layer is a polymer of N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) connected via a b-1,4-glycosidic bond, with each strand being cross-linked …

Advancing Continuous Manufacturing: The Role Of Process Analytical Technology In Process Development, Samuel R. Henson

Electronic Theses and Dissertations

The pharmaceutical industry is actively pursuing technologies which improve manufacturing processes with the goal of producing high-quality pharmaceutical products for patients, manifesting in an industry-wide investment in continuous manufacturing (CM). Process analytical technology (PAT) has been recognized for its successful monitoring of critical quality attributes during routine production and is often cited alongside CM due to its ability to make timely, in-line measurements of intermediate materials. Various PAT tools are valuable in process development, particularly as continuous wet granulation processes are developed for use within pharmaceutical manufacturing. This work applied PAT and chemometric modeling during CM process development to enhance …

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

Analysis Of Adverse Events Associated With Sglt2 Inhibitors And Molecular Mechanisms Using Faers Database And Transcriptome Data, Rahinatu Bawah Ali

USF Tampa Graduate Theses and Dissertations

In this thesis, we explored the differential effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiovascular and renal health, utilizing both clinical data and molecular insights. Focusing on three commonly prescribed SGLT2 inhibitors—Dapagliflozin, Canagliflozin, and Empagliflozin—we employed the Food and Drug Administration Adverse Event Reporting System (FAERS) database to assess adverse events, including myocardial infarction, cardiac failure, tachycardia, acute kidney injury (AKI), renal failure, urinary tract infections, and fungal infections. This analysis was complemented by transcriptomic data from kidney cell lines treated with these drugs, processed through NCBI’s GEO2R and Limma programs, to reveal the gene expression profiles linked to these …

Incorporating Solvation Thermodynamic Mapping In Computer-Aided Drug Design, Yeonji Ji

Dissertations, Theses, and Capstone Projects

Advancements in computational techniques have revolutionized structure-based drug design, substantially improving the efficiency and effectiveness of the drug discovery process by reducing time, costs, and labor requirements. These advancements include various methods, such as investigating small molecule ligands binding to proteins, exploring alternative protein conformations, and solvation mapping on the protein surfaces. Among these methods, understanding the correlation between protein-ligand binding and the role of solvation is important.

A fundamental concept in protein-ligand binding is shape and electrostatic complementarity, which is complicated by the inherent flexibility of proteins. In the absence of small molecule ligands, proteins are complementary to surface …

Gene Expression Analysis Reveals Dysregulation In Traumatic Brain Injury Leading To Tauopathy, Kristina M. Tosi

USF Tampa Graduate Theses and Dissertations

Traumatic Brain Injury (TBI) causes a cascade of detrimental events within neurons, contributing to a host of neurological diseases relating to dementia. In this study we have performed a meta-analysis comparing differentially expressed genes (DEG) in specific cell types such as neurons and microglia revealing inflammation as a common driver of neurological deficiencies post TBI. Inflammation and hypoxia are well characterized features of TBI; however, the molecular mechanisms causing tau hyperphosphorylation by tauopathy associated genes (TAG) post-TBI are currently poorly understood. Furthermore, there are limited in-vitro neuroinflammatory models that mimic primary and secondary TBI. We hypothesize that inducing hypoxia and …

Pharmacodynamic Effects Of Zsj-0228 On Complement Protein Deposition In The Kidneys Of Focal Segmental Glomerulosclerosis-Afflicted Mice., Braeden Pinkerton

Theses & Dissertations

Chronic inflammation, when left untreated, may result in significant morbidity and in severe cases, mortality. While glucocorticoids (GCs) are still being extensively used clinically as a class of very potent anti-inflammatory agents, they are also notorious for diverse adverse side effects. To mitigate these side effects, we have developed a polyethylene glycol (PEG)-based prodrug (ZSJ-0228) of dexamethasone (Dex). When tested on rodent models of Lupus Nephritis and Focal Segmental Glomerulosclerosis (FSGS), ZSJ-0228 was found to provide potent and sustained therapeutic efficacy without any detectable typical GC-associated side effects. Given ZSJ-0228’s transient renal exposure after systemic administration, it is yet to …

Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das

Theses & Dissertations

Over the past decade, the global burden of infectious diseases has increased substantively, underscoring the need for more effective treatment strategies. However, the discovery and development of new drugs with desirable safety, pharmacokinetics, and efficacy is a time consuming and costly process with great uncertainty around success rate. As an alternative to new drug development, prodrugs and novel drug delivery systems have increasingly been explored. Both serve to overcome the drug development challenges. Such drug formulations that permit extended dosing intervals of potent native drugs serve multiple purposes by promoting patient adherence to in improving treatment outcomes. This is especially …

An Ultra Long-Acting Bictegravir Prodrug Nanocrystal With A Shape-Shifting Pharmacokinetic Tail, Mohammad Ullah Nayan

Theses & Dissertations

While antiretroviral therapy (ART) has significantly reduced human immunodeficiency virus type one (HIV-1) co-morbidities and mortality, adherence to daily oral therapy remains a key barrier to all therapeutic and preventative outcomes. Over the past years, the emergence of long-acting (LA) ART has gained considerable enthusiasm amongst people living with HIV (PLWH) and could potentially simplify dosing regimens and improve treatment outcomes. LA ART could also improve drug adherence, reduce viral transmission, and limit viral drug resistance and systemic toxicities. In response to these needs, a combination of two LA injectable nanocrystalline drugs (CABENUVA) was recently approved for bimonthly administration in …

Advancing Text Summarization And Classification: Deep Insights From Transformer-Based Statistical Learning, Kun Bu

USF Tampa Graduate Theses and Dissertations

Artificial Intelligence (AI) is a part of human's daily life nowadays. Machine Learning (ML) as one aspect from AI has been rapidly developing during the past two decades, especially from the statistical learning approaches, which emphasized the use of probability and statistics to model data, such as Support Vector Machines (SVMs) for classification and regression tasks to the ensemble learning techniques, such as Random Forest, Gradient Boosting Machine (GBM), and stacking. Ensemble learning has evolved into a pivotal concept in contemporary machine learning, empowering practitioners to amalgamate multiple models to enhance generalization, accuracy, and robustness. As the field of machine …

The Effects Of Alcohol On Crash Avoidance Reaction Time In A Driving Simulator Task In Humans, Aishwarya Vasudevan

Wayne State University Theses

AIM 1: Alcohol-impaired driving continues to be a significant cause of car crash injuries and deaths. The blood alcohol concentration (BAC) cut-off level for drunk driving is 0.08% in Michigan, and is estimated that lowering this cut-off to 0.05%would save 500–800 lives every year in the US alone. We used a portable virtual reality (VR)-based driving simulator to demonstrate the effects of alcohol at BAC concentrations 0.02-0.08%, grouped into 0.01% increments, on driving performance, specifically Crash Avoidance Reaction Time (CART), i.e., the time (in msec) required to initiate a steering avoidance response. We found that BAC concentrations as low as …

Shedding Light On Ester Drug Metabolism: Investigating Carboxylesterases In Live Cells With Fluorogenic Chemical Tools, Carolyn J. Karns

Masters Theses

No abstract provided.

The Biobehavioral Effects Of Embryonic Exposure To Neural Inflammation And Oxidative Stress In Zebrafish, Dalton J. Anderson

Honors College Theses

The purpose of this research is to improve understanding of the neurodevelopmental effects of embryonic exposure to elevated inflammation and oxidative stress induced by the antipyretic drug acetaminophen (APAP). Our study was the first to examine the interactive effects of APAP and inflammation in zebrafish embryos and how the treatments affect brain development and larval behavior. Experimental groups of zebrafish larvae were exposed to lipopolysaccharide (LPS) to induce inflammation, APAP, or LPS + APAP and larval behavior was analyzed using Ethovision automated behavioral tracking software. We also measured changes in whole-brain Glycogen Synthase Kinase 3 Beta (GSK3B) and GSK3B phosphorylation, …

Delta-9-Tetrahydrocannabinol And Cannabidiol Effect On Dopamine Transporter Expression And Function, Delia M. Guzman

Student Theses

Drug addiction is a major endemic crisis in the United States with a higher prevalence than any other country. Marijuana and hallucinogens make up a great percentage of the drugs of abuse in Americans ranging from 15 to 64 years old. Marijuana contains over 500 active compounds that contribute to its effects, the major components being delta-9-tetrahydrocannabinol (Δ-9-THC) and cannabidiol (CBD). Understanding the pharmacological mechanism as well as the effects that they elicit through the dopaminergic reward system is a key factor in being able to understand why addiction is so prevalent in our society. This research was aimed to …

Elucidation Of Molecular Mechanisms Underlying Novel Multi-Targeted Therapy Strategies For, Qianqian Hu

USF Tampa Graduate Theses and Dissertations

EML4-ALK fusion non-small cell lung cancer (NSCLC) represents a distinct subset of lung cancers that possesses unique molecular and clinical features, paving the way for targeted therapeutic interventions. Despite the promise of ALK-directed therapies, challenges such as metastasis at the time of diagnosis and treatment resistance persist, necessitating deeper research into the underlying mechanisms and potential solutions. In the context of these challenges, our study embarked on two specific objectives. The first goal, elucidated in Chapter 2, revolved around brain metastasis, an event critically facilitated by cell migration. Here, we assessed the anti-migratory activities of several clinical ALK inhibitors in …

Developing A Point-Of-Care Detection Kit For Parkinson’S Disease Using Gold Nanoparticle-Based Lateral Flow Assay, Ali Aljassabi

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease and the fastest-growing neurodegenerative disorder in the world. The major issue with PD is that it takes several years of biological changes until the patient starts to experience physiological symptoms that could affect their daily lives. The major hallmark of PD is the appearance of Lewy body inclusions in the neuron’s cytoplasm, which is rich in a protein called α-Synuclein (α-Syn). Several studies have shown that the levels of α-Syn in blood increase because the excess α-Syn is released from neurons into the bloodstream through extracellular vesicles. …