Medicine and Health Sciences Commons^™

The Synthesis And Characterization Of Ionic Liquids Using Nitrogen-Based Cations For Transdermal Delivery, Jo Galloway

Honors Theses

The purpose of this research was to explore the synthesis mechanisms of water-soluble ionic liquids with nitrogen-containing cationic bases for future use in transdermal drug delivery and forensic science applications. Ionic liquids are salts with an organic cation and either an organic or inorganic anion. They have asymmetric structures, which means that the molecules don’t pack together as neatly as other salts do, therefore, they don’t crystallize as easily, and their melting points are lower. Ionic liquids have melting points below 100°C, and many are liquid at room temperature. Mechanistic studies reveal that the potency of ILs in enhancing transdermal …

Isolation Of Sphingolipids From Sphingomonas Echinoides B-3126 And Their Characterization By Ms/Ms Analysis, Edgar David Uribe Sanchez

Honors Theses

EDGAR DAVID URIBE SANCHEZ: Isolation of Sphingolipids from Sphingomonas echinoides B-3126 and their Characterization by MS/MS Analysis

Sphingolipids are important components in human cellular lipid membranes and are differentiated by the incorporation of serine with an amide bond between the amino acid and a lipid tail. Sphingolipids produced by bacteria differ in both headgroups attached to the serine alcohol and the architecture of the lipid backbone. While the synthesis of sphingolipids in mammalian cells is well studied, only a handful of steps in the pathway are described in bacteria.¹ The observations that although sphingolipid synthesis is rare in bacteria, …

Interrogating Race And Place-Based Inequities In Hiv And Covid-19, Rohan Khazanchi

MD Honors Theses

Over the last four years, I have developed a research focus examining the intersections of race, place, and health. My M.D. Honors Thesis reflects a snapshot of these efforts. In this collection of brief research reports, I leverage area-based measures to investigate structural inequities in three contexts: the HIV epidemic in our hyperlocal community, the early stages of the COVID-19 pandemic, and clinical trials for novel COVID-19 therapeutics. I apply novel social epidemiologic tools to measure and explore disparate outcomes. And, in reflecting upon my findings, I discuss concrete implications for clinicians, researchers, and policymakers alike.

Chapter 1: Neighborhood-Level Deprivation …

Biologically-Inspired Nanoparticles For Oncology Applications, Aishwarya Bapat

Theses & Dissertations

Cancer is the leading cause of death in the United States and its high mortality rate can be attributed towards poor diagnosis methods and less effective therapeutic treatments. Many nanotechnology-based diagnostics and therapeutics are being developed to improve cancer patient outcomes. In this work, we have studied nanoparticles for diagnostic and therapeutic applications in cancer treatment.

In the first work, novel fluorescent NPs loaded with indocyanine green (ICG) were developed for bioimaging applications of pancreatic cancer. Targeted fluorescent nanoparticles (NPs) are being developed to image a range of cancer types with the goal to improve patient outcomes by utilizing in …

Design, Synthesis, And Biological Investigation Of Pyridine Sulfones As Anti-Chlamydia Trachomatis Agents, Mohamed A. Seleem

Theses & Dissertations

Chlamydia trachomatis is the most prominent cause of sexually transmitted bacterial infections worldwide, with around 128 million reported cases annually. This pathogen can cause severe urogenital and ocular consequences, resulting in infertility and trachoma. In its unique developmental cycle, Chlamydia fluctuates between two distinct forms, elementary bodies (EBs) and reticulate bodies (RBs). We hypothesized that caseinolytic protease P (ClpP), a conserved protease among bacterial species, drives the Chlamydia developmental cycle. Earlier work by the Ouellette group demonstrated that Chlamydia relies on its ClpP2 paralogue (ctClpP2) to differentiate between its developmental forms. Dysregulation of ctClpP2 had a significant …

The Development Of Thermoresponsive Hydrogel-Based Drug Delivery Systems For The Treatment Of Musculoskeletal Diseases, Ningrong Chen

Theses & Dissertations

Water-soluble polymers are one of the most commonly used drug delivery vehicles for musculoskeletal diseases. During the past few decades, various biocompatible polymers have been employed in the development of thermoresponsive hydrogels as drug delivery systems for the treatment of local musculoskeletal pathologies. As part of our laboratory’s contribution to this field of study, I have successfully developed three thermoresponsive hydrogel-based formulations for the treatment of three different pathologies associated with the musculoskeletal system.

As my initial effort, I have developed a bone-targeting injectable hydrogel drug delivery system based on Pluronic 127 (Poloxamer 407), which is a Generally Recognized As …

Modulation Of Immune Homeostasis In Neurodegenerative Diseases, Pravin Yeapuri

Theses & Dissertations

Modulating the immune system via. transformation of CD4+ T cell effector to regulatory (Teff to Treg) or promoting microglial clearance of abnormal disease proteins are attractive therapeutic strategies to restore immunological balance in neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease (AD). In the past decade, we defined a safe and effective pathway for Treg induction through the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF was developed in PD animal models and early phase I human studies demonstrating proof-of-concept efficacy for ameliorating disease signs and symptoms. Despite the recorded efficacy, the medicine’s short half-life, limited bioavailability, and injection site reactions …

Polymeric Nanocarriers For Delivery Of Small Molecules Inhibiting Tubulin Polymerization For The Treatment Of Pancreatic Cancer And Lung Metastatic Melanoma, Rajan Sharma Bhattarai

Theses & Dissertations

The aim of this thesis is to develop delivery systems for the novel small molecules which inhibit tubulin polymerization. One of the small molecules was modified to lipid conjugate to increase the lipophilicity of the molecules which in turn drastically improved the drug loading in amphiphilic polymeric system. The second molecule was conjugated to the amphiphilic polymeric backbone with pH sensitive Schiff’s linker for the tumor site specific delivery in lung metastatic melanoma model.

Chapter 1 discusses the tumor microenvironment for the solid tumor especially focusing on Pancreatic Ductal Adenocarcinoma (PDAC). Further the drug delivery system currently researched for addressing …

The Use Of Nebulizer Medications As A Possible Treatment For Covid-19, Jacob Kaufman

Honors College Theses

For the past few years, the COVID-19 pandemic has been the focal point in healthcare and research. This disease has permanently changed daily life and left a historic impact on the world. Most people have felt the effects of this pandemic either directly, via infection, or indirectly, via change in workflow, financial impact, etc. The main question for this virus still remains today; how do we treat this illness effectively? While many ideas are being tested and suggested, a definite answer has yet to be procured. Vaccine rates are climbing on a daily basis, serving as the first and most …

Mississippi Pharmacists’ Perceptions Of Dietary Supplements, Emory Booth

Honors Theses

Dietary supplements are often a controversial topic among healthcare professionals. Many view supplements positively and appreciate the health benefits they can provide. Others are wary of the decreased regulation dietary supplements are subject to and believe that the benefits of supplements do not outweigh the risks. Dietary supplements are of particular interest to pharmacists, as they are often sold at their place of work, and pharmacists have to consolidate their patients’ supplement use with their medication use. The purpose of this thesis is to evaluate the viewpoints of Mississippi pharmacists in relation to dietary supplements. A survey was sent to …

Development Of Bioactive Polymers For Anticancer Sirna Therapy, Siyuan Tang

Theses & Dissertations

Pancreatic ductal adenocarcinoma is a deadly disease with limited treatment options due to late diagnosis and resistance to conventional chemotherapy. Moreover, with the decreased survival rate in the past several years, pancreatic cancer may become the second leading cause of cancer-related death by surpassing breast cancer in 2030. CXCR4/CXCL12 pathway is crucial in tumor-supporting microenvironment, tumor progression, angiogenesis, metastasis and chemotherapy resistance. Small interfering RNA (siRNA) is one of the interfering RNA (RNAi), which targets mRNA specifically then knockdowns the overexpressed oncogene. Thus, siRNA has been widely used as a therapeutic strategy for various diseases including PDAC. In the research …

Sources Of Patient Information For Type 2 Diabetes Self-Care In Northern Mississippi, Minh-Sang La

Honors Theses

Given the prevalence of Type 2 Diabetes Mellitus in the United States and the continuous rise of cases, especially within Mississippi, there is an increasing need to identify if, and how, patients with Type 2 Diabetes receive information about self-care. While there is data available on the topic of where patients receive their information and the influence it has on their health in other countries of the world, the research on the source of Type 2 Diabetes education in the United States is scarce. Therefore, this study aims to bridge the gap of understanding where patients with Type 2 Diabetes …

Content Analysis Of Vitiligo Portrayal On Social Media, Mary Miller

Honors Theses

Given that vitiligo affects a small percentage of the world population, and its affects are not widely known, there is an increasing need to learn of its effects on those with vitiligo, both physical and psychological. Social media has become an influential platform to spread awareness and build confidence in those with vitiligo. This study aims to find how vitiligo is portrayed through social media using content analysis procedures. This is a cross-sectional content analysis that utilized a codebook to analyze Instagram posts. The results were analyzed by interrater reliability and frequency for each coder. The findings of this content …

Firsthand Experience In A Community Pharmacy Through The Lens Of A Pharmacy Technician, Khamariah Patrice Yelder-Anderson

Honors Theses

In the first chapter, I discussed three of the major issues in a community pharmacy which are rude customers, phones, and shorter hours. Technicians have to deal with very opinionated customers who can come off as insolent. The phones are a popular mode of communication for both the patients and physicians but that doesn’t account for the added demands it places on pharmacy workers. Lastly, the pharmacy has experienced later openings with earlier closings that have left filled queues and unhappy customers. The next chapter, interpersonal dynamic, takes a deeper look into how various roles of the pharmacy engage with …

The Design Of A Pcr-Based Assay To Detect And Isolate The Serine Palmitolytransferase Gene From Environmental Bacteria, Lana Taylor

Honors Theses

Sphingolipids are a natural class of lipids that function as structural elements of cell membranes and signaling molecules for important cellular activities such as cell growth, differentiation, apoptosis, recognition, and adhesion. These lipids can be found universally in eukaryotic cells as well as some species of bacteria, such as those found in the human gut microbiome and in the environment in soils. Though sphingolipid production is rare in bacteria, both eukaryotic and prokaryotic sphingolipid biosynthesis begin with the condensation of serine and palmitoyl CoA into 3-ketodihydrosphingosine catalyzed by the enzyme serine palmitoyltransferase (SPT). In recent years, several studies have shown …

Preclinical Development Of A Novel Antileishmanial Agent Ojt007: Bioanalytical Assay, In Vitro Studies And Pharmacokinetics, Maria Eugenia Rincon-Nigro

Dissertations (2016-Present)

Current treatments for cutaneous leishmaniasis suffer from toxic side effects, high cost, parenteral administration, and drug resistance. Thus, there is a critical need to develop oral drugs for the treatment of leishmaniasis. OJT007 is a novel class of drug with potent antiproliferative effects against Leishmania Major. The purpose of this project is to conduct preclinical drug development studies for OJT007 including bioanalytical assay development, pre-formulation studies, in vitro hepatic drug metabolism and in vivo pharmacokinetics. A sensitive, specific, and reproducible ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated. The separation was achieved on a UPLC BEH …

Discovery Of Ojt008 As A Novel Inhibitor Of Mycobacterium Tuberculosis, Collins Chidi Onyenaka

Dissertations (2016-Present)

Despite recent progress in the diagnosis of Tuberculosis (TB), the chemotherapeutic management of TB is still challenging. Mycobacterium tuberculosis (Mtb) is the etiological agent of TB, and TB is classified as the 13th leading cause of death globally [WHO 2021]. 558,000 people were reported to develop multi-drug resistant TB globally [WHO 2020]. Our research focuses on targeting Methionine Aminopeptidase (MetAP), an essential protein for the viability of Mtb. MetAP is a metalloprotease that catalyzes the removal of N-terminal methionine (NME) during translation of protein [Giglione et al., 2003]. This essential role of MetAPs makes this enzyme an auspicious target for …

Discovery Of Ojt010 As A Novel Inhibitor Of Severe Acute Respiratory Syndrome Coronavirus 2, Manvir Kaur

Dissertations (2016-Present)

The current pandemic of coronavirus disease (COVID-19) caused by the highly infectious pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a global public health challenge. The emergence of deadly SARS-CoV-2 variants with mutations on the viral genes has made it more imperative to discover therapeutics that target the host receptors for COVID-19 treatment. Therefore, our research has targeted the critical host entry receptors: Angiotensin-converting enzyme-2 (ACE2) for SARS-CoV-2 entry into the human cells. SARS-CoV-2 is an enveloped RNA beta coronavirus that infects human cells via interaction with the ACE2 receptor, followed by viral replication and virus dissemination. Spike protein …

Patient Harm Associated With Illegal Online Sellers Of Covid- 19 Drug Products: A Year In Review, Kyla Rae Maloney

Undergraduate Honors Thesis Collection

As the online marketplace continues to expand, more patients are turning to the internet for their needs, including COVID-19 pharmaceuticals. However, the current online marketplace is saturated with illegal sellers offering substandard and falsified (SF) products with the potential of causing harm to patients. The primary objective of this thesis is to identify documented cases of harm resulting from illegal online sale of SF COVID-19 related drug or vaccine products. This review utilizes reports by the Medicines Quality Monitoring Globe (MQM Globe) to assess patient harm associated with illegal online sales of COVID-19 marketed pharmaceuticals. This review found 28 references …

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) And Proteomic Evaluation Of Heparin-Binding Proteins From Ajwain (Trachyspermum Ammi) Seeds, Saud Alshammari

Pharmaceutical Sciences (PhD) Dissertations

Trachyspermum ammi, commonly known as ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered. The present study demonstrated the antiproliferative activity of ajwain nsLTP1 in MCF-7, AsPC-1, and MCF10A cell lines and its structural stability in human serum and high-temperature conditions. The antiproliferative activity of ajwain nsLTP1 was evaluated in MCF-7 and AsPC-1 cell lines using an MTT assay. Annexin V-FITC and PI staining were used to detect the …

Content And Activity Of Cytochrome P450 3a In Rat Brain Microsomes And Mitochondria, Nouf Alshammari

Pharmaceutical Sciences (MS) Theses

The potential contribution of CYP3A in brain microsomes and mitochondria is crucial to designing appropriate therapeutic strategies and preventing toxicities. Until recently, there has been limited data reported in the literature with respect to CYP3A activity and its expression in the brain tissue. The reason for this limitation is most likely the relatively low level of CYP3A in the brain tissue. To this end, the primary purpose of this study is to develop a CYP3A functional assay in rat brain mitochondria and microsomes to determine the Michaelis-Menten kinetics of the formation of CYP3A-mediated hydroxylated metabolites of midazolam by UPLC-MS/MS. We …

The Effect Of Covid-19 On Substance Use And Mental Health On A College Campus, Georgia Coffman

Undergraduate Honors Thesis Collection

In this research the authors surveyed a university population to determine the impact COVID-19 has had on substance use and mental health. Current research provides significant data indicating worsening mental health and substance use. This paper looks at how applicable those trends are to a small, private university in Indianapolis, Indiana. The data included 261 respondents composed of students, faculty, and staff of the university. The results reveal college students, faculty, and staff experienced statistically significant increases in feelings of unhappiness, depression, loneliness, hopelessness, agitation, and irritability during the pandemic compared to pre-pandemic. Data analysis of survey responses reveals COVID-19 …

Covid Synergy: A Machine Learning Approach Uncovering Potential Treatment Combinations For Sars-Cov-2, Jason Eden Sanchez

Open Access Theses & Dissertations

For more than two years, the COVID-19 pandemic has upended the lives of billions of individualsworldwide leading to disruptions in healthcare, the economy and society at large. As the pandemic enters its third year, the human impact cannot be overstated and the need to develop effective pharmaceuticals remains. Though there currently exits FDA-approved medications for COVID-19, the emergence of novel variants, such as Omicron, highlights the importance of discovering new therapies which will continue to be effective regardless of the pandemicâ??s progression. Because discovering new medications is a costly and timeintensive endeavor, my approach entails drug repurposing to test medications …

In Vitro And In Vivo Identification And Quantification Of Carmofur And 5-Fluorouracil Using Tandem Mass Spectrometry, Mohammad Mohiminul Islam

Theses and Dissertations

Glioblastoma is the most aggressive solid tumor of the brain. Prior studies from our lab found that carmofur, also known as 1-hexylcarbanoyl 5-fluorouracil (HCFU) is a promising candidate in suppressing and killing tumor cell lines compared to the FDA-approved drug temozolomide. Originally developed as pro-drug of 5-fluorouracil (5-FU), carmofur has been in use in clinic for the treatment of colorectal cancer for over four decades in Japan. Having it used in clinics, it has a high probability of repurposing for diseases with no cure such as glioblastoma. Carmofur has also been found effective against other cancers such as head and …

Effect Of Chemical And Physical Enhancers On The Skin Permeation Of Cromolyn Sodium, Miranda Holman

Electronic Theses and Dissertations

Cromolyn sodium (CS) has clinically shown to be an effective topical remedy for atopic dermatitis, however its physiochemical properties prevent efficient passive drug delivery beyond the outermost skin layer. This project aimed to optimize CS gel formulations and applications to improve drug delivery to the dermis of skin by examining various topical enhancement strategies. Oleic acid, salcaprozate sodium, and microneedles were investigated as enhancers for their effect on skin permeation of CS. In vitro permeation studies across dermatomed porcine ear skin tested CS gels to determine 24-hour drug permeation profiles and skin layer distribution of drug. Further, extraction method efficiency, …

Nanoparticles For Biomedical Applications, Joseph Kim

Dissertations & Theses (Open Access)

This thesis presents development and evaluation of the potential of three new nanoparticles for biomedical applications. With the rapid growth of the field of nanoscience, researchers have explored developing nanoparticles for various biomedical applications, including imaging, therapy, and drug delivery. This thesis demonstrates the development of two C­₆₀ fullerene based nanoparticles and one boron based nanoparticle to answer key questions related to their biological potential.

In the first part of the thesis, we describe synthesis and characterization of a pure boron nanoparticle containing asolectin phospholipid-based liposome construct prepared using a water-in-oil emulsion method, as a novel alternative agent for …

Multimodal Approach To Chronic Pain Management And Prevention Of Opioid Use Disorder, Hannah Elston

The Eleanor Mann School of Nursing Undergraduate Honors Theses

Background. Chronic pain (CP) is a major public health problem that affects one-third of the population and can interfere with the activities of daily life and cause decreased quality of life. Patients with CP have been increasingly prescribed opioids, contributing to the rise in the opioid epidemic. Due to the long-term nature of CP, the use of opioids as the sole treatment for CP can cause tolerance and increased dosages overtime which can lead to addiction and potentially overdose. Therefore, CP treatment should include multimodal approaches to treatment to prevent opioid misuse, opioid use disorder (OUD), and overdose. Multimodal treatments …

Proposing An Educational Framework For Healthcare Professionals On The Topic Of Substandard Or Falsified Medications And Illegal Online Pharmacies, Margo Elaine Whitehead

Undergraduate Honors Thesis Collection

Background: Substandard or falsified medication prevalence in countries like the United States is documented with much more consistency than developing nations. On the contrary, although online pharmacies have been around for several decades, there is very limited data published establishing the prevalence of online pharmacy use by the general population (Fitler). Currently, there is no standardized curriculum regarding substandard or falsified medications and illegal online pharmacies offered to healthcare providers to combat the problems raised by counterfeits. Therefore, it is necessary to assess institutions’ current stance on implementing concepts in the curriculum and to create an educational framework based on …

Investigating Hybrid Cyclic/Linear And Linear Peptides As Vehicles For Nucleic Acid Delivery, Abdulelah Alhazza

Pharmaceutical Sciences (MS) Theses

Small interfering RNA (siRNA) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated Protein 9 (Cas9) are advanced biotechnological approaches that have been able to temporarily downregulate gene expression through post-transcription RNA interference or permanently knockdown a protein via creating a mismatch in DNA, respectively. Nucleic acids are anionic and hydrophilic molecule, which cannot enter the cell through passive diffusion and/or interaction with the cell membrane. Cell-penetrating peptides (CPPs) offer a unique carrier for nucleic acid delivery, where positively charged components of CPP bind to the negatively charged nucleic acid and the hydrophobic components enhance the interaction with cell membrane, and …

Amphiphilic Cyclic Cell-Penetrating Peptides Containing Tryptophan And Arginine As Anticancer Agents And Drug Delivery System, Khalid Zoghebi

Pharmaceutical Sciences (PhD) Dissertations

Amphiphilic cyclic cell-penetrating peptides composed of an increasing number of alternative tryptophan (W) and arginine (R) were synthesized and evaluated as a molecular transporter and for their ability to deliver doxorubicin (Dox) and large molecular weight molecules, such as siRNA and proteins. We prepared a cyclic peptide containing alternative tryptophan (W) and arginine (R) residues and a lysine containing a free side chain amino group. Cyclic peptide [(WR)8WK βA] was conjugated through the free side chain amino group of β-alanine with Dox via a glutarate linker to afford [(WR)8WK]bA-Dox conjugate. The conjugate inhibited the cell viability of ovarian adenocarcinoma (SK-OV-3) …