Chemicals and Drugs Commons^™

Production And Purification Of Basic Fibroblast Growth Factor Fused To Two Collagen Binding Domains Expressed In E. Coli Bl21 Using Flask And Fed-Batch, Hazim Aljewari

Graduate Theses and Dissertations

Delivering effective and non-toxic doses of bioactive materials that can aid in activating tissue regeneration to wounded tissue has proven to be an enormous challenge. This study was designed to produce a potential therapeutic recombinant protein by fusing two collagen binding domains to basic fibroblast growth factors (bFGF) through a collagenase cleavage site linker, so it can release the bFGF in a wound site by the action of this enzyme. The novel fusion protein was expressed in Escherichia coli BL-21 (E. coli) using traditional flask shaker and fed-batch cultivation. Cell lysate was purified by FPLC using Immobilized metal affinity chromatography …

Influence Of Single And Multiple Histidine Residues And Their Ionization Properties On Transmembrane Helix Dynamics, Orientations And Fraying, Fahmida Afrose

Graduate Theses and Dissertations

Since aromatic and charged residues are often present in various locations of transmembrane helices of integral membrane proteins, their impacts on the molecular properties of transmembrane proteins and their interactions with lipids are of particular interest in many studies. In this work, I used solid-state deuterium NMR spectroscopy in designed model peptide GWALP23 [GGALW(LA)6LWLAGA] with selective deuterium labels to addresses the pH dependence and influence of single and multiple “guest” histidine residues in the orientation and dynamic behaviors of transmembrane proteins. The mutations include Gly to His (G2/22 to H2/22), Trp to His (W5/19 to H5/19) and Leu to His …

Assessment Of The Biocompatibilty, Stability, And Suitability Of Natural And Synthetic Polymers And Drugs In The Fda Approval Process, Phuong Anh Hoang Nguyen

Biomedical Engineering ETDs

Regulation of the development, production, marketing, and sales of medical pharmaceuticals and devices in the United States fall under the regulatory functions of the Food and Drug Administration (FDA). The current FDA approval process takes an average of 10 years from start to completion, and costs over $100 million. As a result, companies use many different methods to find additional use of their drugs through marketing directly to the physician, or recycling of previously approved drug moieties. In this work, an evaluation of the in vitro and ex vivo biocompatibility of polymers and drugs in different phases of FDA approval …

Synthesis, Characterization, And Evaluation Of Metal Complexes With Cancer Selective Anti-Proliferative Effects And Hydrogen Evolution Catalytic Properties., Nicholas Vishnosky

Electronic Theses and Dissertations

Bis-thiosemicarbazones (BTSC) and their metal chelates have properties that are useful in several different scientific fields. These systems have already received attention in major fields of biology and engineering. Hydrogen evolution reaction (HER) catalysts need to be cheap and operate under minimal overpotentials with a long lifetime. The treatment of cancer requires, novel agents that have potent cytotoxic activity against cancer cells while displaying minimal side effects. In this dissertation the modular synthesis of these bis-thiosemicarbazone systems is utilized to regulate the redox chemistry for employment in the desired sector of chemistry. The ligand and metal chelates synthesized were characterized …

Iron-Containing Nanoparticles For The Treatment Of Chrionic Biofilm Infections In Cystic Fibrosis, Leisha M. A. Martin

Nanoscience and Microsystems ETDs

Cystic fibrosis (CF) is the most common genetic disease resulting in the morbidity and mortality of Caucasian children and adults worldwide. Due to a genetic mutation resulting in malfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, CF patients produce highly viscous mucus in their respiratory tract. This leads to impairment of the mucociliary clearance of inhaled microbes. In addition to reduced microbial clearance, anoxic environmental conditions in the lungs promote biofilm-mode growth of the pathogenic bacterial species Pseudomonas aeruginosa. Chronic infections of P. aeruginosa begin in early childhood and typically persist until respiratory failure and death result. The …

Development Of In Situ Forming Hydrogels For Intra-Articular Drug Delivery, Andy Prince

Electronic Thesis and Dissertation Repository

Hydrogels are 3-dimensional crosslinked polymer networks that can absorb significant amounts of water. The physical properties associated with hydrogels affords them resemblance to biological tissues making them good candidates for biomedical applications. Many pharmaceuticals, specifically non-steroidal anti-inflammatory drugs (NSAIDs), have poor aqueous solubility, which limits their bioavailability and efficacy. People suffering from chronic osteoarthritis (OA) are required to frequently take large doses to mitigate pain, which can lead to serious side effects. Hydrogels are good strategies to deliver NSAIDs via articular injection because they can form solid gels in situ. This thesis describes the synthesis, formulation, mechanical testing, in …

Multidimensional Mass Spectrometry Of Chemonic™ Ccg-6 Nonionic Surfactant With Separation By Polarity And Shape, Charles Johnson

Williams Honors College, Honors Research Projects

Chemonic™ CCG-6 surfactant is a water-soluble poly(ethylene glycol) (PEG) conjugated alkyl glyceride emollient. This surfactant exists as a complex mixture of a glycerol cores conjugated with poly(ethylene glycol) branches (PEGylation) that were partially esterified with caprylic (C8) and capric (C10) acids. These may be esterified on one, two, or all three arms of the glyceride. The architecture of the structures in this mixture was studied using multidimensional mass spectrometry (MS). Mass spectrometry was interfaced with ultra-performance liquid chromatography (UPLC) and ion mobility (IM) separation. The mixture was separated by reversed-phase LC, oligomers of the star-branched polymer were separated according to …

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D₃ levels have better prognoses than patients with low serum vitamin D_3. However, double-blind clinical trials on the efficacy of vitamin D₃ supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D₃ supplements who had ‘estrogen receptor positive’ …

Removal Of Carbamazepine From Drinking Water, Thomas Krumpolc, Juan Rodriguez, Jordan Alex Gadberry, Zach Wiese, Paola Marrero-Rivera, Adam Johnson

Chemical Engineering Undergraduate Honors Theses

Due to the increasing prevalence of prescription medication over the past few decades, pharmaceuticals have accumulated in various water sources. This has become a public health concern because many pharmaceuticals have limited research on the effects of chronic low-level exposure. According to the World’s Health Organization (WHO), traces of pharmaceuticals products have been reported in different water sources such as surface waters, wastewater, groundwater, and drinking water.^[1] One pharmaceutical of interest that has been detected in water sources is carbamazepine. Carbamazepine (CBZ) is a common pharmaceutical prescribed for the treatment of seizure disorders, neuropathic pain, and various psychological disorders. …

Direct Quantification Of Deubiquitinating Enzyme Activity In Single Intact Cells, Nora Safabakhsh

LSU Doctoral Dissertations

Challenges in drug efficacy occur during the treatment of most types of cancer due to the heterogeneity of the tumor microenvironment. This has led to the development of personalized medicine. Due to the clinical success of the proteasome inhibitors Bortezomib and Carfilzomib in treatment of multiple myeloma, interest has shifted towards molecularly-targeted chemotherapeutics for ubiquitin-proteasome system (UPS). Deubiquitinating enzymes (DUBs) are an essential part of this pathway which have been found to promote Bortezomib resistance in multiple myeloma patients. Unfortunately, there is a lack of specific, high throughput biochemical assays to characterize DUB activity in patient samples before and after …

Preparation Of Supramolecular Amphiphilic Cyclodextrin Bilayer Vesicles For Pharmaceutical Applications, Kate E. Frischkorn

Master's Theses

Recent pharmaceutical developments have investigated using supramolecular nanoparticles in order to increase the bioavailability and solubility of drugs delivered in various methods. Modification of the carbohydrate cyclodextrin increases the ability to encapsulate hydrophobic pharmaceutical molecules by forming a carrier with a hydrophobic core and hydrophilic exterior. Guest molecules are commonly added to these inclusion complexes in order to add stability and further increase targeting abilities of the carriers. One such guest molecule is adamantine combined with a poly(ethylene glycol) chain. Vesicles are formed by hydrating a thin film of amphiphilic cyclodextrin and guest molecules in buffer solution that mimics physiological …

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Developing A Risk Assessment Protocol To Quantify Distribution And Uptake Of Persistent Organic Pollutants In Glacial Outflows, Kimberley Rain Miner

Electronic Theses and Dissertations

Pollutants released by industrialized nations between 1960 and 2004 have been transported northward through atmospheric processes and deposited into glaciated alpine ecosystems. Many of these chemicals retain their original structure and are absorbed into the biota thousands of miles away from where they were originally utilized. With a warming climate increasing the melt of alpine glaciers, these glaciers may be introducing growing amounts of toxins into the watershed. While studies have demonstrated the existence of resident pollutants within glaciated ecosystems, no one has developed a risk assessment to identify sources and quantity of risk posed by these compounds when released …

The Development Of Microfluidic Devices For The Production Of Safe And Effective Non-Viral Gene Delivery Vectors, Jason Matthew Absher

Theses and Dissertations--Chemical and Materials Engineering

Including inherited genetic diseases, like lipoprotein lipase deficiency, and acquired diseases, such as cancer and HIV, gene therapy has the potential to treat or cure afflicted people by driving an affected cell to produce a therapeutic protein. Using primarily viral vectors, gene therapies are involved in a number of ongoing clinical trials and have already been approved by multiple international regulatory drug administrations for several diseases. However, viral vectors suffer from serious disadvantages including poor transduction of many cell types, immunogenicity, direct tissue toxicity and lack of targetability. Non-viral polymeric gene delivery vectors (polyplexes) provide an alternative solution but are …

The Effects Of Emerging Technology On Healthcare And The Difficulties Of Integration, Skyler J. Pavlish-Carpenter

Honors Undergraduate Theses

Background: Disruptive technology describes technology that is significantly more advanced than previous iterations, such as: 3D printing, genetic manipulation, stem cell research, innovative surgical procedures, and computer-based charting software. These technologies often require extensive overhauls to implement into older systems and must overcome many difficult financial and societal complications before they can be widely used. In a field like healthcare that makes frequent advancements, these difficulties can mean that the technology will not be utilized to its full potential or implemented at all.

Objective: To determine the inhibiting factors that prevent disruptive technology from being implemented in conventional healthcare.

Methods: …

Fabrication And Modification Of Titania Nanotube Arrays For Harvesting Solar Energy And Drug Delivery Applications, Ahmed El Ruby Abdel Rahman Mohamed

Electronic Thesis and Dissertation Repository

The fast diminishing of fossil fuels in the near future, as well as the global warming caused by increasing greenhouse gases have motivated the urgent quest to develop advanced materials as cost-effective photoanodes for solar light harvesting and many other photocatalytic applications. Recently, titania nanotube arrays (TNTAs) fabricated by anodization process has attracted great interest due to their excellent properties such as: high surface area, vertically oriented, highly organized, one-dimensional, nanotubular structure, photoactivity, chemical stability and biocompatibility. This unique combination of excellent properties makes TNTAs an excellent photoanode for solar light harvesting. However, the relatively wide band gap energy of …

Magnetic Field-Induced Intramolecular Cyclization As A Trigger For Nanoparticle-Based Delivery Systems., Sara Katherine Biladeau

Electronic Theses and Dissertations

Magnetic nanoparticles (MNPs) are used in a variety of applications, including as agents for magnetic resonance imaging, generation of local hyperthermia, and as platforms for drug delivery. Iron-based MNPs are often coated with a shell, such as silica or gold, to increase biocompatibility for drug delivery applications. Many MNPs used for cancer therapy rely on either an internal trigger, such as a difference in pH, or an external trigger, such as light or an alternating magnetic field (AMF), to cause release of a payload, typically a chemotherapeutic drug. Internal triggers are appealing because drug release can be targeted to a …

Characterization Of Murine Breast Cancer Cell Lines For Anti-Cancer Vaccine, Haven N. Frazier

Biological Sciences Undergraduate Honors Theses

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer death among women in the United States (1). While treatments involving radiation and chemotherapy currently exist, disease must be detected early in order for the treatments to be somewhat effective, and there is no effective treatment after metastasis occurs (2). Additionally, current therapies do not mitigate tumor immunosuppression. Decreasing the tumor-associated immunosuppressive conditions while activating antitumor immunity could prevent recurrence and metastasis, possibly leading to an effective treatment for cancer (3). Tumor cell vaccines could possibly address this issue and have become a …

Micellular Electrokinetic Chromatography For Studying Amyloid Beta Oligomer Membrane Affinity, Andrew Bryson

Biomedical Engineering Undergraduate Honors Theses

Amyloid Beta (Aβ) was the major focus of this study. It is a peptide that is present in the brain with a high tendency to self-aggregate. When this protein aggregates, it forms oligomers and protofibrils which in turn are deposited as senile plaques in the brain. The reason for the concern with these plaques is their association with the neurological disorder Alzheimer’s disease. It has been found that the most dangerous oligomers are formed in a portion of the plasma membrane known as lipid rafts. The purpose of this study was to understand how micelles affect the aggregation properties of …

An In Vivo Study Of The Effects Of Perinatal Caffeine Exposure On Synaptic Efficacy In The Hippocampus Of Freely Moving Adult Rats, Jee Eun Park

Senior Theses and Projects

The synapse from the perforant path to the dentate gyrus has been widely used successfully to demonstrate long-term potentiation, a cellular model underlying learning and memory. Caffeine is one of the most widely consumed psychoactive stimulants in the world. Caffeine consumption increases in alertness, improvements in motor skills, and neurological functions, and these effects have promoted its use throughout history. Although the many short term cognitive benefits of caffeine intake are well understood, the long term effects of caffeine exposure have been widely disputed. Despite this, it is estimated that over 80% of women continue to consume caffeine throughout pregnancy. …

Acid-Base Equilibria In Organic-Solvent/Water Mixtures And Their Relevance To Gas/Particle Partitioning In The Atmosphere And In Tobacco Smoke, Julia Lynn Degagne

Dissertations and Theses

Acid-base equilibria in organic particulate matter (PM) are poorly understood, but have important implications for air quality and public health. First, acid-base reactions in organic particulate matter affect the gas/particle partitioning of organic compounds in the atmosphere, and these processes are not currently represented in atmospheric and climate change models. Second, the acid-base balance of tobacco smoke affects the amount of nicotine absorbed by the smoker, and a greater understanding of this balance would help to relate cigarette smoke composition to the addictive properties of cigarettes. This work presents data related to both air quality and tobacco smoke modeling.

The …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick

Doctoral Dissertations

The goal of this dissertation was to parse the roles of physical, mechanical and chemical cues in the phenotype plasticity of smooth muscle cells (SMCs) in atherosclerosis. We first developed and characterized a novel synthetic hydrogel with desirable traits for studying mechanotransduction in vitro. This hydrogel, PEG-PC, is a co-polymer of poly(ethylene glycol) and phosphorylcholine with an incredible range of Young’s moduli (~1 kPa - 9 MPa) that enables reproduction of nearly any tissue stiffness, exceptional optical and anti-fouling properties, and support for covalent attachment of extracellular matrix (ECM) proteins. To our knowledge, this combination of mechanical range, low …

Engineering Approaches For Suppressing Deleterious Host Responses To Medical Implants, Connor Mccarthy

Dissertations, Master's Theses and Master's Reports

Small diameter (< 6 mm) vascular grafts suffer from serious deleterious effects not encountered with their larger diameter relatives, leading to premature graft failure through restenosis. Platelet activation, inflammation, and smooth muscle cell proliferation are leading contributors to thrombosis and neointimal hyperplasia, both contributors to the progression of restenosis. It may be possible to suppress negative biological responses to vascular implants through the modification of surface properties and incorporation of drug release into blood contacting materials. In this work, bioengineering approaches are presented to improve the biocompatibility of small diameter vascular grafts.

We demonstrate a novel engineering approach for incorporating natural, decollagenized elastin matrices into PEU 1074A reinforced vascular grafts through spray-coating and electrospinning processes in a manner that retains elastin’s excellent blood contacting properties. A vascular construct with excellent mechanical and surgical handling properties demonstrating the suppression of neointimal hyperplasia is presented after 21 days in vivo.

Nitric oxide (NO) has been investigated over the past several decades due to its platelet, inflammation, and smooth muscle cell suppressing effects; and if appropriately delivered, could positively mediate the contributors to restenosis. Here, we characterize a novel macrocyclic NO …

Polymer Interactions With Nucleic Acids Under Various Physiological Conditions, Matthew S. Obrzut

Williams Honors College, Honors Research Projects

The goal of this project is to improve our understanding of nucleic acid interactions with cationic polymers with the theory that the polymers could protect the nucleic acids from degradation caused by biological enzymes. We seek to understand what the limitations of the cationic polymers are which, in this case, is mainly polymer-DNA compatibility. This experiment utilized peptide-dextran hybrid polymers with differing functionalizations to condense anionic nucleic acids into nanometer-sized polyplexes. Techniques of dynamic light scattering and zeta-potential were utilized to determine the particle sizes and surface charges of polyplexes.

In this experiment, dextran with a molecular weight of 20 …

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Poly(Ester Amide) And Poly(Ethyl Glyoxylate) Nanoparticles For Controlled Drug Release, Amira Mohamed Moustafa

Electronic Thesis and Dissertation Repository

The objective of this research was to develop polymeric nanoparticles (NPs) having improved drug release properties for drug delivery. Poly(ester amide)s (PEAs) are promising biodegradable polymers. PEA NPs were prepared via emulsification-evaporation and salting-out methods and optimized through by varying different processing parameters. Polymer-model drug conjugates based on PEAs containing L-aspartic acid and rhodamine B were synthesized and used for NP preparation. Release behavior was studied and compared to a control system with physically encapsulated rhodamine B. It was shown that the release of rhodamine B from the covalent system did not show the burst effect and exhibited a slower …

Assessment Of Similarity In Chemically Complex Samples, Jessica Elise Brown

Dissertations and Theses

Concern within the public health community is mounting regarding what some deem as "candy-flavored tobacco". A recent study by King et al. (2014) found that >40% of middle and high school student smokers use flavored cigarettes or flavored little cigars. This study investigated the validity of the "candy-flavored tobacco" designation by comparing flavor profiles of 18 flavored tobacco products with 15 candy and Kool-Aid products using gas chromatography mass spectrometry (GC/MS). Significant compositional overlap was found; nearly 75% of the compounds detected were present in at least one flavored tobacco and one candy or Kool-Aid product. Benzaldehyde and or benzyl …

Anti-Gd2 Etoposide-Loaded Immunoliposomes For The Treatment Of Gd2 Positive Tumors, Brandon S. Brown

Dissertations & Theses (Open Access)

Systemic chemotherapeutics remain the standard of care for most malignancies even though they frequently suffer from narrow therapeutic index, poor serum solubility, and off-target effects. Monoclonal antibodies that specifically bind antigens overexpressed on many tumors such as the ganglioside, GD2, can be conjugated to drug-loaded liposomes to create a targeted drug delivery system. In this study, we have encapsulated etoposide, a topoisomerase inhibitor effective against a wide range of cancers, in surface modified liposomes decorated with anti-GD2 antibodies. We characterized the properties of the liposomes using a variety of methods including dynamic light scattering, electron microscopy, and Fourier transformed infrared …

The Effects Of Ocean Acidification And Eutrophication On The Growth, Lipid Composition And Toxicity Of The Marine Raphidophyte Heterosigma Akashiwo., Julia Rose Matheson

Electronic Thesis and Dissertation Repository

Anthropogenic forcing, such as ocean acidification caused by rising carbon dioxide emissions, and eutrophication due to increased nutrient loadings in run-off, are causing major changes to the biogeochemistry of the oceans. As a consequence, coastal phytoplankton are susceptible to altered biogeochemical environments. This study examined the effect of a lower pH and increased levels of nutrients on the common coastal harmful alga, Heterosigma akashiwo. Growth rates, maximal cell yields, neutral lipid accumulation and toxicity of cells grown under various pH and nutrients regimes were measured. H. akashiwo growth was near maximal when grown at lower pH levels. There was …