Pharmacy and Pharmaceutical Sciences Commons^™

A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang

Pharmacy Faculty Articles and Research

Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa …

Evaluation Of Anemia In Communities Served By Shoulder To Shoulder Global: A Cross-Sectional Study In Santo Domingo, Ecuador, Kevin J. Mercer, Daniela Claudia Moga, Steven Fleming, Cristian Carrión, Melody Ryan

Pharmacy Practice and Science Faculty Publications

Background Shoulder to Shoulder Global (STSG) recognizes anemia as a cause of morbidity among patients in Santo Domingo, Ecuador. Little research has been done to assess targetable anemia risk factors to serve as a foundation for future pharmacotherapeutic interventions. This study sought to characterize anemia in this population to lay the foundation for future preventive intervention.

Methods Cross-sectional data obtained from existing clinic records from 2010 to 2016 included hemoglobin/hematocrit, age, sex, pregnancy status, and respective community. Chi-square compared means to examine risk factors associated with anemia. Logistic regression and odds ratios (OR) were used to estimate risk factors associated …

Tungsten-Enhanced Breast Cancer Metastasis To The Bone Is Associated With Alterations In The Bone Niche., Cameron J. Chock, Alicia Bolt

Pharmaceutical Sciences ETDs

The objective of this thesis project was to investigate the effects of tungsten on breast cancer metastasis to the bone niche, using the 4T1 orthotopic breast cancer model. Oral tungsten (15 ppm) exposure did not affect primary tumor growth. However, following tungsten exposure there were marked changes in the bone niche, including increased metastasis of 4T1 tumor cells and increased osteolysis. Further analysis of the bone niche indicates that enhanced metastasis is associated with a pro-tumorigenic immune suppressive environment, including increased number of granulocytic myeloid derived suppressor cells and increased gene expression of the pro-inflammatory cytokine IL-1β and the activated …

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, …

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 …

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 …

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 …

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 …

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 …

Akt Inhibition In The Central Nervous System Induces Signaling Defects Resulting In Psychiatric Symptomatology, Apostolia-Maria Tsimberidou, Antonis Skliris, Alan Valentine, Jamie Shaw, Ursula Hering, Henry Hiep Vo, Tung On Chan, Roger S Armen, Jeffrey R Cottrell, Jen Q Pan, Philip N Tsichlis

Center for Translational Medicine Faculty Papers

Background: Changes in the expression and activity of the AKT oncogene play an important role in psychiatric disease. We present translational data assessing the role of AKT in psychiatric symptoms.

Methods: (1) We assessed the protein activity of an AKT3 mutant harboring a PH domain mutation (Q60H) detected in a patient with schizophrenia, the corresponding AKT1 mutant (Q61H), and wild-type AKT1 and AKT3 transduced in AKT-null mouse fibroblasts and modeled the Q61H mutation onto the crystal structure of the Akt1 PH domain. (2) We analyzed the results of earlier genome-wide association studies to determine the distribution of schizophrenia-associated single-nucleotide polymorphisms …

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 …

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 …

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 …

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 …

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 …

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 …

A State-Wide Education Program On Opioid Use Disorder: Influential Community Members' Knowledge, Beliefs, And Opportunities For Coalition Development, Lindsey Hohmann, Haley Phillippe, Karen Marlowe, Ruth Jeminiwa, Natalie Hohmann, Salisa Westrick, Amanda Fowler, Brent Fox

College of Pharmacy Faculty Papers

Background: Deep South states, particularly Alabama, experience disproportionately higher opioid prescribing rates versus national rates. Considering limited opioid use disorder (OUD) providers in this region, collaborative efforts between non-healthcare professionals is critical in mitigating overdose mortality. The Alabama Opioid Training Institute (OTI) was created in 2019 to empower community members to take action in combatting OUD in local regions. The OTI included: 1) eight full-day in-person conferences; and 2) an interactive mobile-enabled website ( https://alabamaoti.org ). This study assessed the impact of the OTI on influential community members' knowledge, abilities, concerns, readiness, and intended actions regarding OUD and opioid overdose …

Synthesis Of Fluorinated Ketones For Biological Evaluation At The Gaba-B Receptor, Katherine Kreusel

Honors Theses

The proper functioning of the CNS depends on the balance between excitatory and inhibitory neurotransmitters. While excitation is primarily regulated by glutamate, inhibition is regulated by γ-aminobutyric acid (GABA). When GABA binds to a GABA receptor, there is a block in nerve transmission which is important when studying pain and drug addiction. There are two types of GABA receptors that are used as drug targets: GABA-A and GABA-B. While GABA-A receptors are ionotropic and ligand-gated ion channels, GABA-B receptors are G-protein coupled receptors that are used by cells to convert extracellular signals into intracellular responses. Although many therapeutics modulate the …

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 …

Airborne And Dermal Collection Methods Of Gunshot Residue For Toxicity Studies, Samuel Cole Smith, Oscar Beau Black, Courtney Roper

Faculty and Student Publications

Gunshot residue (GSR) has potential negative health effects on humans as a result of inhalation and dermal exposure to the chemical and physical characteristics of GSR such as Pb, Sb, Ba, nitrocellulose, nitroglycerine, and particulate size fraction. Filter (size selective) and double-sided tape (non-size selective) samples collected airborne GSR during single and triple firing of a 0.22 caliber revolver. Dermal exposures were considered using hand swabs and de-leading wipes, designed to remove the heavy metals. The samples underwent analysis to investigate physical (morphology, size distribution, zeta potential), chemical (black carbon and element concentrations), and potential to induce oxidative stress (oxidative …

Isolation Of Echimidine And Its C-7 Isomers From Echium Plantagineum L. And Their Hepatotoxic Effect On Rat Hepatocytes, Michał Gleńsk, Marta K. Dudek, Peter Kinkade, Evelyn C.S. Santos

Faculty and Student Publications

Echimidine is the main pyrrolizidine alkaloid of Echium plantagineum L., a plant domesti-cated in many countries. Because of echimidine’s toxicity, this alkaloid has become a target of the European Food Safety Authority regulations, especially in regard to honey contamination. In this study, we determined by NMR spectroscopy that the main HPLC peak purified from zinc reduced plant extract with an MS [M + H]+ signal at m/z 398 corresponding to echimidine (1), and in fact also represents an isomeric echihumiline (2). A third isomer present in the smallest amount and barely re-solved by HPLC from co-eluting (1) and (2) was …

Development Of Α-Tocopherol Succinate-Based Nanostructured Lipid Carriers For Delivery Of Paclitaxel, Sushrut Marathe, Gauri Shadambikar, Tabish Mehraj, Suresh P. Sulochana

Faculty and Student Publications

The management of retinoblastoma (RB) involves the use of invasive treatment regimens. Paclitaxel (PTX), an effective antineoplastic compound used in the treatment of a wide range of malignant tumors, poses treatment challenges due to systemic toxicity, rapid elimination, and development of resistance. The goal of this work was to develop PTX-loaded, α-tocopherol succinate (αTS)-based, nanostructured lipid carrier (NLCs; αTS-PTX-NLC) and PEGylated αTS-PTX-NLC (αTS-PTX-PEG-NLC) to improve ocular bioavailability. The hot homogenization method was used to prepare the NLCs, and repeated measures ANOVA analysis was used for formulation optimization. αTS-PTX-NLC and αTS-PTX-PEG-NLC had a mean particle size, polydispersity index and zeta potential …

Essential Oil Yield, Composition, And Bioactivity Of Sagebrush Species In The Bighorn Mountains, Valtcho D. Zheljazkov, Charles L. Cantrell, Ekaterina A. Jeliazkova, Tess Astatkie

Faculty and Student Publications

Sagebrush (Artemisia spp.) are dominant wild plants in large areas of the U.S., Canada and Mexico, and they include several species and subspecies. The aim was to determine if there are significant differences in essential oil (EO) yield, composition, and biological activity of sagebrush within the Bighorn Mountains, U.S. The EO yield in fresh herbage varied from 0.15 to 1.69% for all species, including 0.25–1.69% in A. tridentata var. vaseyana, 0.64–1.44% in A. tridentata var. tridentata, 1% in A. tridentata var. wyomingensis, 0.8–1.2% in A. longifolia, 0.8–1% in A. cana, and 0.16% in A. ludoviciana. There was significant variability in …

Fractionation Of Sulfated Galactan From The Red Alga Botryocladia Occidentalis Separates Its Anticoagulant And Anti-Sars-Cov-2 Properties, Seon Beom Kim, Mary Zoepfl, Priyanka Samanta, Fuming Zhang

Faculty and Student Publications

Sulfation pattern and molecular weight (MW) play a key role in the biological actions of sulfated glycans. Besides anticoagulant effects, certain sulfated glycans can also exhibit anti-SARS-CoV-2 properties. To develop a more selective antiviral carbohydrate, an efficient strategy to separate these two actions is required. In this work, low MW fractions derived from the red alga Botryocladia occidentalis sulfated galactan (BoSG) were generated, structurally characterized, and tested for activity against SARS-CoV-2 and blood coagulation. The lowest MW fraction was found to be primarily composed of octasaccharides of monosulfated monosaccharides. Unlike heparin or native BoSG, we found that hydrolyzed BoSG products …

A Simple, Cost-Effective, And Green Hptlc Method For The Estimation Of Ascorbic Acid In Solvent And Ultrasound-Assisted Extracts Of Phyllanthus Emblica, Capsicum Annuum, And Psidium Guajava, Ahmed I. Foudah, Prawez Alam, Faiyaz Shakeel, Aftab Alam

Faculty and Student Publications

Greener analytical methodologies for the estimation of ascorbic acid (AA) are poorly reported in the literature. Furthermore, the green indexes of the literature’s analytical assays of AA estimation have not been assessed. As a consequence, the aim of this research is to invent and validate a simple, cost-effective, and green reverse-phase “high-performance thin-layer chromatography (HPTLC)” method for the estimating AA in the solvent extracts (SE) and ultrasound-assisted extracts (UAE) of Phyllanthus emblica, Psidium guajava, and Capsicum annuum. The greener mobile phase for AA estimation was a binary mixture of water and ethanol (70:30, v/v). At a wavelength of 265 nm, …

Rap1a Activity Elevated The Impact Of Endogenous Ages In Diabetic Collagen To Stimulate Increased Myofibroblast Transition And Oxidative Stress, Stephanie D. Burr, Christopher C. Dorroh, James A. Stewart

Faculty and Student Publications

Diabetics have an increased risk for heart failure due to cardiac fibroblast functional changes occurring as a result of AGE/RAGE signaling. Advanced glycation end products (AGEs) levels are higher in diabetics and stimulate elevated RAGE (receptor for AGE) signaling. AGE/RAGE signaling can alter the expression of proteins linked to extracellular matrix (ECM) remodeling and oxidative stressors. Our lab has identified a small GTPase, Rap1a, that may overlap the AGE/RAGE signaling pathway. We sought to determine the role Rap1a plays in mediating AGE/RAGE changes and to assess the impact of isolated collagen on further altering these changes. Primary cardiac fibroblasts from …

Selective Inhibition Of Plasmodium Falciparum Atpase 6 By Artemisinins And Identification Of New Classes Of Inhibitors After Expression In Yeast, Catherine M. Moore, Jigang Wang, Qingsong Lin, Pedro Ferreira

Faculty and Student Publications

Treatment failures with artemisinin combination therapies (ACTs) threaten global efforts to eradicate malaria. They highlight the importance of identifying drug targets and new inhibitors and of studying how existing antimalarial classes work. Here, we report the successful development of a heterologous expression-based compoundscreening tool. The validated drug target Plasmodium falciparum ATPase 6 (PfATP6) and a mammalian orthologue (sarco/endoplasmic reticulum calcium ATPase 1a [SERCA1a]) were functionally expressed in Saccharomyces cerevisiae, providing a robust, sensitive, and specific screening tool. Whole-cell and in vitro assays consistently demonstrated inhibition and labeling of PfATP6 by artemisinins. Mutations in PfATP6 resulted in fitness costs that were …

Synthesis, Characterization, And Evaluation Of Amphiphilic Cell-Penetrating Peptides As Sirna Delivery Tools For Cancer Therapy, Muhammad Imran Sajid

Pharmaceutical Sciences (PhD) Dissertations

Post-transcriptional gene silencing (PTGS), also termed as RNA interference (RNAi) possess a great therapeutic potential. Three siRNA-based products have been recently approved that have developed a renewed interest in the scientific community to explore this alternative therapeutic area rigorously. However, several challenges are limiting their use as a widespread therapeutic agent. The limitations include their membrane impermeability, short half-life, elimination by the kidney, entrapment by the reticuloendothelial system, sequestration by plasma proteins, endosomal trap, and off-target effects.

Several delivery systems and transfection agents have been investigated to address these challenges. Still, most of the systems suffer from toxicity and low …