Chemicals and Drugs Commons^™

Modeling Sex-Specific Changes In Myocardial Fibrosis, Grace Martin

Chemical Engineering Undergraduate Honors Theses

Heart disease the leading cause of death for both men and women in the United States. Cardiac fibrosis, or accumulation of extracellular matrix proteins in the heart, can occur after a heart attack and increase the risk for further complications. Current treatments for heart disease do not include extracellular matrix regulators, partly due to the complicated signaling network responsible for the production of these proteins. By using a computational model of the signaling network in cardia fibroblasts, the relationship between particular molecules and downstream extracellular matrix production can be examined.

Biological sex is an important factor for cardiac health and …

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Photodynamic Therapy To Treat Triple Negative Breast Cancer In Vitro, Hunter S. Warren

All Theses

Triple negative breast cancer (TNBC) is the most resilient form of breast cancer, being one of the leading causes of death for women and making up 7% of all cancer deaths. Photodynamic therapy (PDT) offers a minimally invasive solution to TNBC as a passive-targeting treatment that reduces the need for other well established yet harsh treatments that can be taxing on the patient. PDT involves the use of a high-energy red light on the area of a tumor injected with photosensitizers (PS) that generate reactive oxygen species (ROS) in the tumor, triggering cell death. The PS tetra(hydroxyphenyl)chlorin (m-THPC) was used …

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …

Development Of A New Affinity Membrane For Rapidly Purifying Non-Antibody Proteins, Friendship Edioma

All Theses

This thesis project describes the modification and evaluation of a new affinity membrane for rapid chromatographic purification of non-antibody proteins. The affinity membrane utilizes Im7/CL7 coupling technology developed by Dr. Vassylyev's lab at the University of Alabama Birmingham (UAB), licensed by TriAltus Bioscience. The behavior of the membrane was evaluated using purified CL7-tagged Cas9 as my model protein for static and dynamic binding capacity analysis.

Chapter one provides an overview on biopharmaceutical drug production process development. I discuss how protein drugs are produced, isolated, and purified from the cell supernatant after upstream phases are completed. Despite increasing demands for biologics, …

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 …

Drug-Facilitated Sexual Assault At The University Of Arkansas, Barrett Weidman

Chemical Engineering Undergraduate Honors Theses

This work was written to fulfill two main purposes. First, to help survivors of Drug-Facilitated Sexual Assault (DFSA) process their experience by compiling the toxicological, pharmacological, and distribution of the three most used date-rape drugs. Second, to gauge the knowledge and interest of University of Arkansas students regarding drug impairments, sexual assault education, and bystander intervention training. A survey was conducted for the latter and revealed that 91.6% of students believe the University’s existing sexual assault prevention education and bystander intervention training have room for improvement. Also, 37.1% of students who have received this education report that the programming does …

Alternative Fixation Of Venous Valves For Bioprosthetic Applications, Makenzie Kapales

Biomedical Engineering Undergraduate Honors Theses

Venous valve failure allows for the retrograde, or backward, flow of blood into the lower extremities, which leads to Chronic Venous Insufficiency (CVI). CVI infringes upon quality of life through ulceration and can result in death due to Deep Vein Thrombosis (DVT), or blood clots, causing pulmonary embolism. A successful treatment of CVI restores valve function and prevents retrograde blood flow; however, current bioprosthetic venous valves exhibit low patency and high calcification. To improve upon bioprosthetic venous valves and CVI treatment, the University of Arkansas’s Cardiovascular Biomechanics Lab conducts studies with the purpose of comparing the properties and performance of …

Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko

Theses and Dissertations

Respiratory distress syndrome (RDS) is characterized by shortness of breath and low oxygen levels. RDS affects the neonatal and adult populations. In the neonatal population, RDS can be classified as NRDS (Neonatal respiratory distress syndrome), while in adults, it is known as ARDS (acute respiratory distress syndrome). This dissertation examines a therapeutic approach to NRDS and a mechanistic approach to ARDS with in vivo and in vitro models of lung injury. NRDS is characterized by a deficiency or lack of surfactant. Surfactant is an essential compound composed of phospholipids and proteins to prevent the lungs from collapsing. There are several …

Characterization Of Nanoparticles Using Inductively-Coupled Plasma Mass Spectrometry, Jabez D. Campbell

MSU Graduate Theses

Nanomaterials are a relatively new class of materials that have many applications which span a wide host of fields from medical products to consumer products. The possible compositions and forms of nanomaterials are just as varied as the applications. Therefore, a versatile characterization method is needed for researchers and regulators alike to ensure nanomaterials are properly used. Single Particle Inductively Coupled Plasma Mass Spectrometry (SP-ICP-MS) is a functional method that could fill the characterization need in the nanomaterial research field. Using data from both SP-ICP-MS tests and data from literature established characterization methods, the viability of making SP-ICP-MS the standard …

Itraconazole Nanocomposites Prepared Via Rotary Evaporator Drying Of Nanomilled Suspensions, Alexander Santos Coelho

Theses

The aim of this study is to explore the feasibility of rotary evaporation for drying wetmilled drug suspensions as a novel approach to produce drug nanocomposites that exhibit fast redispersion and immediate drug release. To this end, the physical stability of the nanomilled itraconazole (drug) suspensions, a.k.a., nanosuspensions, during the milling and storage; the drying of the itraconazole nanosuspensions via the rotary evaporator; and the type/loading of various polymers/surfactants (dispersants) on aqueous redispersion and drug release from the nanocomposites were examined. Our results suggest that smaller drug particle size, owing to nanomilling, and smaller nanocomposite particle size, owing to optimized …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

Machine Learning Applied To Colloidal Properties Of Perfluorocarbon Nanoemulsions For Imaging In Ards/Ali, Marco Hosfeld

Electronic Theses and Dissertations

Acute Respiratory distress Syndrome (ARDS) and Acute Lung Injury (ALI) are inflammatory lung pathologies consisting of non-hydrostatic pulmonary edema leading to hypoxia and impaired gas exchange in the lungs. ARDS/ALI is both difficult to study and treat as it is not in itself a specific pathology but rather a syndrome consisting of many pathologies that vary case by case. It is, however, consistently characterized by an explosive acute inflammatory response in the lung parenchyma leading to hypoxia. Although time has seen to an increase in the understanding of ARDS/ALI, the mortality rate remains in the range of 30-50%. For these …

Zein And Lignin-Based Nanoparticles As Delivery Systems: Pesticide Release And Nanoparticle Health Impact On Soybean Plants, Fallon Polette Salinas Gonzalez

LSU Doctoral Dissertations

This research examined the effect of biodegradable, polymeric, lignin-based nanoparticles (LNPs, 113.8±3.4, negatively charged) and zein nanoparticles (ZNP, 141.6±3.9, positively charged) on soybean plant health. The LNPs were synthesized from lignin, covalently linked to poly(lactic-co-glycolic) acid by emulsion evaporation. ZNPs were synthesized by nanoprecipitation. Soybeans grown hydroponically were treated with three concentrations (0.02, 0.2, and 2 mg/ml) of NPs at 28 days after germination. The effect of ZNPs and LNPs on plant health was determined through analysis of root and stem length, chlorophyll concentration, dry biomass of roots and stem, as well as carbon, nitrogen, and micronutrient absorption after 1, …

Liposomal Delivery Of Remdesivir For Localized And Targeted Treatment Of Covid-19, Anupama Melam

McKelvey School of Engineering Theses & Dissertations

Liposomal delivery of Remdesivir for localized and targeted treatment of COVID-19

COVID-19 is a serious, and in many cases lethal, disease that is caused by infection of the upper respiratory tract by the novel betacoronavirus, SARS-Cov-2 virus. This disease has a very high mortality rate and has affected the world in a global pandemic. SARS-Cov-2 binds to the ACE2 receptor via the receptor-binding domain (RBD) in the S protein. After this, the virus fuses with the cell membrane by the formation of a six-helix bundle. Thus, the S protein plays a major role in ensuring that the virus attaches to …

Additive Manufacturing In Personalized Medicine: Patient-Customized Solid Dose Medicines, And Patient-Customized Wound Care Device, Amir Najarzadeh

Theses and Dissertations--Mechanical Engineering

Personalized Medicine - from a one-size fits all to a tailored approach is the future in pharmaceutical therapeutics and medical applications. The aim of this study is demonstrate additive manufacturing in two personalized medicine applications: 1. Patient- customized solid dose medicines, and 2. Patient-customized wound care device. The aim of the first application is to develop an inexpensive and accurate method to design and fabricate patient-customized tablets. Particularly this paper focuses on fabricating and dose controlling of patient-customized extended release prednisolone-poly(vinyle alcohole) PVA. Dry-Blending, Wet Granulation, Extrusion, Spherionization, Hot melt extrusion (HME) was adopted to produce drug loaded prednisolone-PVA filaments …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Assessment Of The Use Of Low Molecular Weight Diblock Copolymers For The Formation Of Stable, Tunable Droplet Interface Bilayers, Joseph Tawfik

Masters Theses

This thesis presents the use of diblock copolymers, poly(butadiene)-b-poly(ethylene oxide) (PB_m PEO_n) and poly(isoprene)-b-poly(ethylene oxide) (PI_mPEO_n), as amphiphilic molecular building blocks for the formation of synthetic polymer bilayer membranes using the droplet interface bilayer (DIB) technique. The DIB technique makes use of the self-assembly of amphiphilic macromolecules along oil-water droplet interfaces that can then be physically connected for the construction of liquid supported macromolecular bilayers at the droplet interface. These bilayer membranes are capable of hosting both naturally occurring and synthetic protein channels. This technique has been used to form synthetic bilayer membranes …

Development Of Water-Soluble Polyesters For Tissue Engineering Applications, Trent Gordon

Electronic Thesis and Dissertation Repository

The development of tunable polymers has become increasingly important for both tissue engineering and drug delivery. This thesis investigates the development of water-soluble polyesters that contain both natural and synthetic components. These polymers offer tunable chemical structures, as well as functional groups for the conjugation of crosslinking moieties or cell signaling molecules. The first series of polymers was synthesized from poly(ethylene glycol) (PEG) and aspartic acid (Asp) via a titanium catalyzed transesterification method to provide polymers with molar masses of 12 kg/mol. After deprotection, the pendent functional groups of Asp were reacted with methacrylic, maleic, and itaconic anhydride to introduce …

Nature-Inspired Electrode Materials For Next Generation Sustainable Energy Storage, Mikhail Miroshnikov

Dissertations, Theses, and Capstone Projects

Despite revolutionizing the world of portable electronics, the contemporary lithium-ion battery (LIB) suffers from challenges associated with the cost, safety, and environmental impact of transition metal oxide-based intercalation cathodes. To alleviate these issues, naturally occurring organic molecules may serve as sustainable alternatives to traditional inorganic cathode materials. The electrochemical properties of organic compounds are derived from redox-active functional groups containing oxygen, nitrogen and sulfur. Additionally, these functional groups are capable of coordinating metal ions beyond lithium, allowing for compatibility with sodium-ion batteries (SIBs) and other earth abundant metal-based energy storage systems. However, despite competitive performance against commercialized cathode materials, much …

Screening And Characterization Of A Pan-Gtpase Inhibitor, Leyla Akhadov

Biomedical Engineering ETDs

Abnormal functioning of small GTPases is implicated in a variety of diseases, ranging from neurological and developmental diseases to cancer. In fact, mutant GTPases are found in up to 30% of cancers. Thus, small GTPases are a highly relevant target in drug discovery and development. High-throughput targeted screening of small molecules is the most productive method of discovering compounds that can give insights into drug development. This thesis describes improvements made to a high-throughput GTPase-targeted screening method to minimize confounding systematic error. It also describes the follow-up characterization of a compound that was identified in a high-throughput screen. The compound …

Does Circularizing Source-Separated Food Waste Present A Risk To Our Food?, Astha Thakali

Electronic Theses and Dissertations

About a third of the food produced annually is wasted. Food waste recycling can be a way to close the loop and attain a more sustainable food system, however, the system must be carefully monitored and managed to avoid the introduction and build-up of contaminants. To study the potential presence of contaminants in food waste, source-separated food waste was collected and screened for five classes of contaminants (physical contaminants, heavy metals, halogenated organic contaminants, pathogens, and antibiotic resistance genes) from two separate regulatory environments (voluntary vs mandated food separation). The regulatory environment did not affect the level of contamination, except …

Peptoid And Antibody-Based Gfp Sensors, Solomon Isu

Graduate Theses and Dissertations

In this work, we have made and characterized a pair of immunobiosensors for detecting the green fluorescent protein (GFP) in an aqueous matrix. An anti-GFP antibody-based biosensor was assembled to detect GFP, while a novel peptoid (N-substituted oligomers of glycine designated as IOS-1) biosensor was also assembled for GFP detection. A quartz crystal microbalance (QCM) gold sensor was used as the supporting substrate for self-assembly of the immunobiosensors. Gravimetric measurements of the QCM gold sensor during immunobiosensor construction and operation were available in real-time using a QCM instrument. X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and Fluorescence microscopy were used …

Engineered Nanoparticles For Site-Specific Bioorthogonal Catalysis: Imaging And Therapy, Riddha Das

Doctoral Dissertations

Bioorthogonal catalysis offers a strategy for chemical transformations complementary to bioprocesses and has proven to be a powerful tool in biochemistry and medical sciences. Transition metal catalysts (TMCs) have emerged as a powerful tool to execute selective chemical transformations, however, lack of biocompatibility and stability limits their use in biological applications. Incorporation of TMCs into nanoparticle monolayers provides a versatile strategy for the generation of bioorthogonal nanocatalysts known as “nanozymes”. We have fabricated a family of nanozymes using gold nanoparticles (AuNPs) as scaffolds featuring diverse chemical functional groups for controlled localization of nanozymes in biological environments, providing unique strategies for …

Gesea Biosciences - Core Shell Pellet Manufacturing Device, Claire Edelman, Maria Medrano, Rachel Longoria

Biomedical Engineering

No abstract provided.

Experimental And Computational Tools For Single Cell Analysis In Cancer Diagnostics, Manibarathi Vaithiyanathan

LSU Doctoral Dissertations

Substantial evidence shows that cellular heterogeneity commonly exists within an isogenic or clonal population. Whether in isolation or caused through a combination of the above events, cellular heterogeneity can dramatically influence cellular decision making and cell fate, however, this can be masked by the average response from a population. One approach to solve this issue is to analyze a population at the individual cell level. The goal of this work is to develop high-throughput experimental and computational platforms to screen and quantify single cancer cells for specific intracellular enzyme activities. An interdisciplinary approach was taken to 1) better understand the …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

Functional Importance Of Lipin Phosphorylation, Stephanie Elizabeth Hood

Graduate Theses and Dissertations

Highly conserved throughout evolution, lipins are dual functioning proteins found from yeast to humans. Functioning in the cytoplasm as phosphatidate phosphatase enzymes (PAP), lipins produce diacylglycerol that serves as a precursor for neutral fats and membrane phospholipids. Alternatively, nuclear lipins are responsible for the regulation of metabolic genes. Interestingly, both the mammalian lipin 1 paralog and the single Drosophila Lipin ortholog are highly phosphorylated proteins. Target of rapamycin (TOR) has previously been identified as one of the kinases that controls the subcellular localization of both lipin 1 and Drosophila Lipin. However, other serine and threonine kinases are predicted to be …