Pharmacy and Pharmaceutical Sciences Commons^™

Quality By Design Based Optimization Of Anti-Inflammatory Nanoemulgels For Local Treatment Of Burn Wounds, Leah Dickey

Electronic Theses and Dissertations

Burns are some of the most traumatizing and damaging skin injuries, with the potential of causing extensive internal damage that increases the risk of chronic wound development. Oral and topical analgesics in combination with antibiotics can provide temporary relief and improve wound healing progress for both mild and severe burns. However, recurrent systemic exposure to pain relievers and antibiotics has been associated with adverse side effects including nausea, drowsiness, abdominal pain, etc., and increased risk of new infections or even ulcers. Local and targeted drug delivery systems, such as nanomedicine, have gained attention as potentially more effective alternatives to improve …

Prevalence And Predictors Of Polypharmacy In Adolescents Who Have Engaged In Sexually Abusive Behaviors, Rebecca Gilley

Electronic Theses and Dissertations

Polypharmacy, or the concurrent use of multiple medications, is associated with detrimental outcomes for patients and has gathered increasing attention within the scientific clinical literature. Pediatric populations warrant special consideration for the practice of polypharmacy, as medication effects are more pronounced in youth and adverse effects may have a lasting impact on development. This dissertation study examined psychotropic prescribing practices in a sample of adolescents who have engaged in sexually abusive behaviors, a subset of justice-involved youth who are at risk for polypharmacy. General prescribing trends were examined, and a principle components analysis involving variables associated with risk of polypharmacy …

Development Of Anti-Inflammatory Theranostic Nanocolloids Using Quality By Design Approaches, Michele Herneisey

Electronic Theses and Dissertations

Nanocolloids are attractive delivery vehicles for drugs with poor aqueous solubility. Despite this, relatively few nanocolloid products exist on the market. Currently, there is a lack of standardization in the pre-clinical, academic setting regarding nanocolloid development and quality control testing. Adaptation of quality by design (QbD) methods used in the pharmaceutical industry to nanocolloid development is a desirable approach that can improve nanocolloid product and process understanding, resulting in an increased number of marketable products.

The central hypothesis of this work is that QbD approaches can be utilized to optimize theranostic (therapeutic and diagnostic) nanocolloid stability, drug loading, and imaging …

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, …

Immune-Related Adverse Events Of Immune Checkpoint Inhibitors: Incidence, Risk Factors, Clinical Outcomes, And Economic Burden In Older Adults With Non-Small Cell Lung Cancer, Yiran Rong

Electronic Theses and Dissertations

To fill the gap in existing literature related to immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC), this dissertation focused on: 1) assessing the incidence, spectrum and risk factors for the development of irAEs; 2) assessing the clinical impact of irAE occurrence on survival and treatment discontinuation; 3) analyzing and estimating the incremental economic burden of irAEs among an older population in the United States (US). A retrospective cohort study was conducted using the SEER-Medicare 2020 linkage database in order to evaluate the three study objectives. The dissertation included 8,175 patients diagnosed …

Polymeric Nanovaccine Delivery System For Influenza Vaccine, Chaitanya K. Valiveti

Electronic Theses and Dissertations

Vaccines are the most efficient and cost-effective method for preventing illnesses caused by infectious pathogens. Even though the great success of vaccines over decades, the development of safe and robust vaccines is still essential for emerging new pathogens, re-evolving old pathogens, and improving the insufficient protection given by existing vaccines. One of the most critical strategies for developing effective new vaccines is selecting and using a suitable adjuvant or immune stimulant. Immunologic adjuvants are essential for improving vaccine potency by enhancing the immune response of vaccine antigens. The amount of antigen could be spared with improved potency, especially during mass …

Design, Synthesis, Structure Optimization, Structure-Activity Relationship (Sar), And Biological Evaluation Of Novel And Potent Thiazolo[4,5-D]Pyrimidine Corticotropin Releasing Factor (Crf) Receptor Antagonists, Md Rabiul Islam

Electronic Theses and Dissertations

No abstract provided.

Design And Synthesis Of Fused Pyrimidines As Single Agents With Combination Chemotherapy Potential, As Tubulin Polymerization And One-Carbon Metabolism Inhibitors For Cancer, Tasdique Quadery

Electronic Theses and Dissertations

This dissertation describes the design, synthesis, and biological evaluation of bicyclic fused pyrimidines as single agents with combination chemotherapy potential with both antiangiogenic and cytotoxic effects. The dissertation also discusses one-carbon metabolism inhibitors and tumor targeting proteolysis targeting chimeras (PROTACs).

In cancer chemotherapy, the two major limitations are the dose-limiting toxicities of clinically used agents and the development of resistance to the treatment. Combination chemotherapy with antiangiogenic agents and microtubule targeting agents has shown an advantage against both these drawbacks. Single agents with both antiangiogenic activity and cytotoxicity would afford a therapy that circumvents pharmacokinetic problems of multiple agents, avoid …

Decreasing Unintentional Pregnancies For Tennesseans, Paula M. Todd

Electronic Theses and Dissertations

In 2018, 49% of all pregnancies in the United States were unintended, with women with a lower- income status being five times more likely to experience an unplanned pregnancy. Tennessee has a high rate of unintended pregnancies, particularly among the uninsured, low-income, and rural teen populations; some 22% of these unintended pregnancies end in abortion. Oral or transdermal contraceptives that are affordable and accessible for women of childbearing age can reduce unintentional pregnancies. The addressed gap in clinical practice was that contraceptives are not currently available over the counter in Tennessee pharmacies without a prescription, which necessitates a costly medical …

Development Of A Combined Feedforward-Feedback Quality Control System For Extended-Release Granules Using A Quality By Design Approach, Yuxiang Zhao

Electronic Theses and Dissertations

Objectives

For a fluid bed film coating process to consistently deliver quality products, its control system needs to be robust against the variability of input materials and environmental disturbances. Presently, limited studies have been reported to understand the effects and interactions of the material attributes, environmental variables, and process parameters on the product in vitro drug dissolution. A control system can be developed with a proper understanding of the coating process, by adjusting the process parameters in feedback and feedforward manners to compensate for the undesired effect caused by disturbances, and ensure consistent product quality.

Methods

The control system was …

The Role Of Mek1/2 And Mek5 In Melatonin-Mediated Actions On Osteoblasts And Osteoclasts Differentiation, Bone Formation, Bone Microarchitecture, And Bone Biomechanics, Fahima Akter Munmun

Electronic Theses and Dissertations

Melatonin, the main endogenous hormone to entrain the circadian system, is not limited to its role in regulating the sleep-wake cycle; rather, it affects a wide variety of systems involving antioxidant, anti-inflammation, blood pressure regulation, seasonal reproduction, ovarian physiology, and immune function. Driven by the diversity of its action, melatonin for a long time has also been studied in the field of bone and mineral research both clinically and pre-clinically. Exogenous administration of melatonin in clinical trials in perimenopausal women (MOPS; NCT01152580); or postmenopausal women with osteopenia (MelaOST; NCT01690000 and MOTS; NCT01870115) confirmed improvement of bone mineral density (BMD) (MelaOST; …

Towards A "Universal Chemical Biology Toolbox" For Tackling Human Diseases, Christopher Swank

Electronic Theses and Dissertations

A lack of new drug targets and drug mechanisms, coupled with drug-pipeline attrition, represent significant problems in oncology drug discovery. Towards addressing this challenge, “fully-functionalized small-molecule probes” (FFSMPs) have been established, which are compounds that can be immediately used as “bait” to capture their protein targets under the same assay conditions used for oncology-based phenotypic screening. Specifically, each FFSMP library member contains one or more structural-diversity elements to promote interactions of the probe with different protein targets in living cells, an electrophile or photoreactive functional group for covalent attachment of the probe to interacting proteins via affinity or photoaffinity labeling, …

Histone Deacetylases In Alcohol Associated Liver Disease., Srineil Bodduluri

Electronic Theses and Dissertations

Alcohol abuse is endemic worldwide and there is no FDA approved treatment for Alcohol-Associated Liver Disease (ALD). Many scholars have posited that targeting Histone Deacetylases (HDAC) may be therapeutic in ALD intervention. In this study, the changes in hepatic gene expression and immune phenotyping of mice undergoing chronic plus binge alcohol exposure was examined. The characterization of relative mRNA levels for all 18 HDAC were performed. Results showed decreased expression of the genes HDAC 1,7,9,10,11 and Sirtuin enzymes (SIRT) 3,4,5,7. Other pathways related to lipid metabolism as well as systemic inflammation and hepatic injury also exhibited significant changes. These altered …

Clinical Pharmacy Services And Medication Utilization In Hospice Care, Aishwarya Kulkarni

Electronic Theses and Dissertations

Background: As discussed within the guidelines from the American Society of Health-System Pharmacists (ASHP), pharmacists are an integral part of the hospice multidisciplinary team involved in optimizing the treatments. Methadone, a long-active opioid, is particularly useful in this population but may be clinically underutilized. Additionally, the cost share of medication utilization in hospice and palliative care is shifting towards hospice providers. The assessment of medication utilization and methadone use in this setting can help develop overall cost/clinical optimization strategies. Thus, there is a need to understand the use and expenditure of various medications and pharmacists' role in providing methadone …

Pde4 Inhibition: A Novel Therapeutic Strategy In Liver Fibrosis., Mohamed Elnagdy

Electronic Theses and Dissertations

Background: Liver fibrosis is accumulation of extracellular matrix (ECM) proteins due to chronic liver injury. Chronic hepatic damage can occur due to multiple causes including, alcohol, non-alcoholic steatohepatitis and chronic viral hepatitis. Liver fibrosis is a critical problem worldwide due to the extremely high incidence of alcohol associated liver damage and chronic viral hepatitis. Moreover, there is no FDA approved therapy for liver fibrosis. Activation and transdifferentiation of quiecent hepatic stellate cells (HSCs) to myofibroblasts (MFBs) is the main event contributing to liver fibrosis. This process involves two phases, the initiation and the perpetuation phases. Hepatocyte injury and inflammatory response …

The Role Of Src In Nsclc Cell And Lung Fibroblast Migration On 3d Cell-Derived Matrix., Austin M Krueger

Electronic Theses and Dissertations

Lung cancer is responsible for the most cancer deaths between males and females, with a 6% five-year survival rate. Cancer metastasis is one of the leading causes of lung cancer lethality. Our lab has developed a method to culture cells on cell-derived matrix (CDM) and study cell-ECM interactions. This study utilized multiple cell migration methods to investigate the migration of NSCLC cells and IMR90 lung fibroblasts, both together and independently, on 2D plastic and 3D CDM. Our results showed that inhibiting Src, a significant influencer of cell migration and member of integrin activation, blocked cancer cell migration on 2D and …

The Place And Role Of Pharmacy Benefit Management (Pbm) Companies In Us Healthcare System, George Mattis Ii

Electronic Theses and Dissertations

On average, prescription drugs cost US consumers more than any other developed country in the world. US drug makers claim that intermediaries in the prescription drug supply chain, companies called pharmacy benefit managers (PBM), are forcing them to increase their drug prices. PBMs counter that the discounts they receive from drug makers are channeled to insurers. This thesis will examine the role that PBMs play in the prescription drug supply chain and determine what effect they have on drug prices. This thesis will utilize a comparative static model, Structure, Conduct, Performance (SCP) framework to analyze the pharmaceutical manufacturing and the …

Development Of Thiol Specific Fluorogenic Benzofurazan Derivatives For Live Cell Subcellular Organelle Thiol Imaging, Shenggang Wang

Electronic Theses and Dissertations

No abstract provided.

Design, Synthesis, And Evaluation Of Glutathione Derivatives As Brain Targeting Agents, Yue Huang

Electronic Theses and Dissertations

Treatment of central nervous system (CNS) diseases, such as Alzheimer’s disease, Parkinson’s diseases, and brain tumors, is still a challenge due to the existence of the blood-brain barrier (BBB). The BBB as a membrane barrier that separates systemic blood circulation from the CNS is structurally formed by endothelial cells, astrocyte, pericyte and neurons and is one of the crucial protection mechanisms for the CNS. The BBB protects the brain by preventing foreign compounds (non-endogenous compounds) from entering the brain and helps maintain brain homeostasis. In addition, the presence of drug efflux pumps (i.e., P-glycoproteins, multidrug-resistance proteins) in the BBB helps …

Isolation Of Marker Compounds From Copaiba Essential Oil And Mimosa Pigra For Quality Evaluation Of Dietary Supplements, Mohammed Hawwal

Electronic Theses and Dissertations

Natural products have been used as a primary means of treating illness since ancient times, and they remain an important pool of U.S. FDA approved drugs. Approximately 33% of all current pharmaceutical medications discovered between 1981 and 2014 are either natural products or derived from natural products (Newman and Cragg 2016). The process of isolating specialized metabolites from medicinal plants has led to the development of particularly important medicines worldwide (Rakotomalala, Agard et al. 2013) such as Taxol® from Taxus brevifolia Nutt. (Taxaceae) and salicylic acid from the bark of Salix spp. This research is composed of five chapters; the …

A Role For The Hydroxybenzoic Acid Metabolites Of Flavonoids And Aspirin In The Prevention Of Colorectal Cancer, Ranjini Sankaranarayanan

Electronic Theses and Dissertations

Flavonoids are a group of polyphenolic compounds, with established antioxidant properties, that are present ubiquitously in plants, fruits, and vegetables. Their universal presence in nature is evident by the fact that more than 4000 types of flavonoids have been identified till date. Additionally, they have also become part of the daily diet through consumption of fruits such as berries, grapes, pomegranate, and cherries, and vegetables such as onions, kale, and eggplant. High levels of flavonoids are also consumed through beverages such as tea and red wine. Numerous studies have demonstrated that a diet rich in flavonoids decreases the incidences of …

Responses Of Predatory Myxobacteria To Prey Signaling Molecules & Features Of A Pseudomonas Prey Avoiding Predation, Shukria Akbar

Electronic Theses and Dissertations

Gram-negative unicellular myxobacteria, along with their multicellular lifestyle andbiologically active specialized metabolites, are known for the predatory interactions with Gram-negative/ Gram-positive bacteria and fungi. Although myxobacterial predation range have been exploited extensively, little is known about the prey associated molecules contributing to myxobacterial predator-prey dynamics. By employing transcriptomics and untargeted metabolomics approaches, we demonstrate two structurally distinct classes of signaling molecules from Gram-negative bacterial prey elicit significant omics responses from myxobacteria, Myxococcus xanthus and Cystobacter ferrugineus. An overlapping and general response to acylhomoserine lactones, whereas a distinctive response to a quinolone signaling molecule is observed from both myxobacteria. Similarly, by …

Responses Of Myxobacteria To Plant-Related Chemosignals Suggests Their Roles In The Rhizobiome, Barbara Iyare Adaikpoh

Electronic Theses and Dissertations

In the rhizosphere, plants curate and maintain distinct rhizobiome, some of which serve as secondary defense mechanisms against pathogenic microorganisms. Additionally, in response to biotic stress, plants generate phytohormones which regulate signaling pathways to activate systemic resistance. These phytohormones contribute to the chemical space within the rhizosphere in addition to other low-molecular-weight metabolites used for cell-to-cell communication within species and across kingdoms. However, little is known about the influences of stress-related phytohormones on beneficial bacteria even though biocontrol strategies abundantly explore plant-beneficial microorganisms to manage pathogens in agricultural systems. Myxobacteria are competent predators of plant pathogens and have demonstrated responses …

Influence Of Rage Signaling On Cellular Communication In Diabetes-Mediated Vascular Calcification, Amber Michelle Kennon

Electronic Theses and Dissertations

Chronic hyperglycemia is one of the main characteristics of type 2 diabetes mellitus (T2DM). With the increased prevalence of T2DM, the risk of cardiovascular complications, including heart attack or stroke, is increased. Complications linked to the vasculature are increased vascular calcification (VC) or mineral deposition within the medial layer of conducting arteries. Under calcification conditions, vascular smooth muscle cells (VSMCs) undergo an osteogenic switch to an osteoblast-like cell and begin producing bone proteins. Chronic hyperglycemia can also result in increased extracellular matrix (ECM) synthesis, accumulation, and crosslinking. One of the cell types responsible for increased ECM synthesis are ‘activated’ fibroblasts …

Development Of Ibuprofen Tablet With Polyethylene Oxide Using Fused Deposition Modeling (Fdm) 3d Printing Coupled With Hot-Melt Extrusion, Sooyeon Chung

Electronic Theses and Dissertations

Ibuprofen is known to plasticize several polymers used in the pharmaceutical field, and it is considered challenging to achieve an immediate release by fused deposition modeling (FDM). Therefore, this study aimed to print ibuprofen tablet with a focus on achieving immediate release. Polyethylene oxide (Polyox WSR N80) was used as a main matrix to form the ibuprofen filament due to its water-soluble property and manifesting suitable mechanical property even with the high drug loading (40% w/w). Several release modifiers such as Kollidon VA64, Kollidon 12PF, Kollicoat IR, Kollidon CL, and Mannitol were added separately to the formulation to enhance the …

Rap1a Overlaps The Age/Rage Signaling Cascade In Type 2 Diabetes Mellitus, Stephanie Burr

Electronic Theses and Dissertations

Diabetic individuals have an increased risk for developing cardiovascular disease due to stiffening of the left ventricle, which is thought to occur, in part, by increased AGE/RAGE signaling. Advanced glycation end products (AGEs) accumulate within the body over time, and under hyperglycemic conditions, the formation and accumulation of AGEs is accelerated. AGEs exert their effect by binding to their receptor (RAGE) and can induce myofibroblast differentiation, oxidative stress, cell-extracellular matrix contraction, and cell migration. Previous findings from our lab have demonstrated that preventing the production of Rap1a, a Ras-like GTPase signaling protein, in cardiac fibroblasts will decrease type 2 diabetes …

Methylene Blue As Light And Reactive Oxygen Species Sensitive Ligand: Appicability In Hybrid Drug And Material Synthesis, Huy Dao

Electronic Theses and Dissertations

Methylene blue (MB) with a 10-N-carbamoyl linkage was discovered and developed as a multifunctional far-red (660 nm) photocleavable ligand capable of rendering a series of MB conjugated compounds with off-to-on fluorescence switch properties through the controlled release of MB. The released MB was successfully demonstrated to be an effective photosensitizer, imaging probe, and therapeutic agent. The complete release of MB was achieved with a cumulative light dose of 15 J/cm2. The photosensitivity was demonstrated to be dependent on the type of chemical bond at 10-N of the phenothiazine ring which links MB to a side group. Specifically, the urea bond-based …

Hot-Melt Extrusion Based Fused Deposition Modeling 3d Printing Of Atorvastatin Calcium Tablets: Impact Of Shape And Infill Density On Printability And Performance, Preethi Mandati

Electronic Theses and Dissertations

The main objective of the current research is to investigate the effect of shapes (heart and round shape tablets) and infill densities (50% and 100%) on drug release profiles of tablets prepared by hot melt extrusion (HME) coupled fused deposition modeling (FDM) technique. Two different commercial FDM 3D printers with different filament feeding mechanisms were evaluated for suitability of printing. Drug-loaded filaments of 1.5 mm and 2.5 mm diameters were extruded using Process 11 mm HME, using atorvastatin as a model drug and Kollicoat® IR, Kollidon® VA64, Kollidon®12PF, and Kolliphor® P407 as hydrophilic polymers. Filaments of Kollicoat® IR in combination …

Subcutaneous Delivery Of Albumin, Vy Nguyen

Electronic Theses and Dissertations

An increasing number of protein drugs are used in the clinic to treat a broad range of diseases. However, because of their large molecular sizes and high hydrophilicity, protein drugs are not orally bioavailable, which commonly require intravenous, intramuscular or subcutaneous injection. Thermosensitive polymers have been widely investigated as in situ depots for sustained drug release delivered through subcutaneous route.Albumin is the most abundant proteins in bloodstream. It has long half-life (19 days in human) and plays important roles such as acting as carrier for fatty acids, amino acids, waste products and medical compounds. Albumin has been studied for decades …

Metal-Organic Frameworks As Bacteria Mimicking Delivery Systems For Tuberculosis, Ailin Guo

Electronic Theses and Dissertations

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M.tb), with an estimated 1.5 million deaths and 10 million infections each year. Although TB can be effectively treated with antibiotics, because of the complications and length of treatment, many people fail to complete the treatment which exacerbates the emergence of drug-resistant M. tb strains. The goal of this work is to develop biomimetic particles as host-directed therapy to target the infected macrophages. Two types of metal-organic frameworks (MOFs), MIL-100(Fe) and MIL-88A(Fe) were developed for bacteriamimicking particles. As a proof-of-concept, Mannose was selected as a ligand to target macrophages because …