Medicine and Health Sciences Commons^™

Mechanism Of Interaction Of Peptide Modified Nanoparticles With Porphyromonas Gingivalis., Ankita Jain

Electronic Theses and Dissertations

Studies suggest that P. gingivalis functions as a keystone pathogen and interacts with primary colonizers in the supragingival biofilm such as S. gordonii. This interaction contributes to the initial colonization of the oral cavity by P. gingivalis and thus represents a potential target for therapeutic intervention. We have identified a peptide (BAR) derived from the streptococcal SspB protein that functions to inhibit P. gingivalis adherence to S. gordonii. In addition, we showed that nanoparticles (NPs) functionalized with BAR inhibit this interaction more potently than free soluble peptide, possibly by promoting interaction with P. gingivalis at higher valency than …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

An Investigation Into Formulation And Therapeutic Effectiveness Of Nanoparticle Drug Delivery For Select Pharmaceutical Agents, Dustin Cooper

Electronic Theses and Dissertations

Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug delivery systems. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Furthermore, polymer based, biodegradable nanodelivery has become increasing popular in the field of NP formulation because of their high degree of compatibility and low rate of toxicity. Due to their popularity, commercially available polymers such as poly lactic acid (PLA), poly glycolic acid (PGA) and polylactic-co-glycolic acid (PLGA) are commonly used in the development and design of new nano based delivery …

Novel Cellular Targets Of Aspirin In Chemoprevention Studies On P53, G6pd And C-Myc, Guoqiang Ai

Electronic Theses and Dissertations

Background

Aspirin has generated a significant interest in recent years as a potential chemopreventive agent supported by strong evidence from epidemiological data; however, the mechanisms are not well understood. The objective of this dissertation is to identify novel cyclooxygenase (COX)-independent pathways by which aspirin exerts its anticancer effects in epithelial cancer cell lines. We investigated the effect of aspirin on p53, glucose 6-phosphate dehydrogenase (G6PD), and c-Myc, all of which are known to play a major role in cancer development. p53 is a tumor suppressor protein, often mutated in cancers causing its inactivation. Expression of G6PD is elevated in many …

Measuring And Understanding Health-Related Quality Of Life Among Adult Patients With Hemophilia, Ruchit Mukesh Shah

Electronic Theses and Dissertations

Objectives: The objectives of this study are to: 1) examine the psychometric properties of the Medical Outcomes Study Short Form-12 Version 2 (SF-12v2); 2) assess the measurement invariance of the SF-12v2 with respect to age, disease severity, and treatment regimen; 3) identify psychosocial predictors of health-related quality (HRQOL) among adults with hemophilia in the United States. Methods: This cross-sectional study was conducted using both a web-based and paper-based self-administered survey. Adults with hemophilia were recruited using an online panel, a Facebook community of hemophilia patients, and at the University of Mississippi Medical Center hemophilia treatment clinic. Psychometric properties of the …

Exploring New Chemical Entities From Traditional Medicine: Docking, Synthesis And Specific Bioactivities, Chinni Yalamanchili

Electronic Theses and Dissertations

Traditional medical systems contributed significantly to medicine with a number of their phytochemicals found to possess good biological properties. Recently, Dr. Youyou Tu was awarded the Nobel Prize (2015) for her discovery/isolation of Artemisinin from the TCM plant Artemisia annua. Our first aim is to identify active phytochemicals against botulinum neurotoxin A (BoNT/A), and diabetes from Ayurveda and TCM, respectively, by using in silico, in vitro and in vivo approaches. In our second aim, we wanted to enantioselectively synthesize scalable quantities of phytoestrogenic isoflavans such as equol and sativan. The following three chapters summarize results of the three research goals. …

Critical Quality Attributes Of Topical Semi-Solid Dosage Forms: Solvent Activity, Muralikrishnan Angamuthu

Electronic Theses and Dissertations

Critical quality attribute has been defined as “a physical, chemical, biological or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality”. Deviations from preset quality metrics may potentially result in drug products with inferior therapeutic efficacy and unacceptable clinical safety profile. Topical cream formulations may possess numerous quality attributes that can affect the permeation of the drug through skin and consequently therapeutic efficacy. CQAs of topical formulations are often aimed at characterizing either the physicochemical properties of APIs or bulk characteristics of the formulation itself. Solvent systems constitute a …

Novel Approaches For Ungual And Trans-Ungual Delivery Of Drugs, Avadhesh Singh Kushwaha

Electronic Theses and Dissertations

Topical therapy is commonly used for the treatment of nail diseases such as onychomycosis and nail psoriasis due to less severe side effects, non-invasiveness, direct drug delivery at the site of infection, patient compliance and lower cost of treatment. However, topical treatment is limited due to poor permeability and hard nature of nail plate. The main objective of first project was to investigate the penetrability of apremilast into and across the nail plate, folloby the preparation of a novel nail lacquer formulation to improve its ungual and trans-ungual permeation for the treatment of nail psoriasis. Dexpanthenol and salicylic acid were …

Biological And Chemical Investigation Of Panamanian Plants For Potential Utility Against Metabolic Syndrome, Yelkaira Vasquez

Electronic Theses and Dissertations

Metabolic syndrome (MetS) affects approximately 25% of the adult population of the world and represents a public health concern with high socioeconomic impact worldwide. Latin American populations exhibit a high prevalence of MetS, similar or even higher than developed countries. This complex and progressive disorder can develop over many years as a cluster of conditions characterized by a constellation of metabolic abnormalities. Specific guidelines have not yet been established for the treatment of MetS per se. The increased prevalence of MetS has been associated with a greater risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In …

Role Of Microglial Α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator In Neuroinflammatory Pain Models In Mice, Muzaffar Abbas

Electronic Theses and Dissertations

Neuroinflammatory pain affects about 1.5% of the United States population. Around 20-40% patients having neurological disorders are affected with neuroinflammatory pain. As a part of the limbic system, hippocampus is known to play a critical role in pain perception and processing, and is densely populated with microglial cells and α7 nicotinic acetylcholine receptors (nAChRs). Given the role of microglial α7 nAChRs in neuroinflammation, the α7 nAChRs have emerged as potential target for neuroinflammatory pain treatment. We hypothesized that microglial α7 nAChRs positive allosteric modulation in the hippocampus will decrease neuroinflammatory pain at behavioral, cellular, biochemical, and molecular level. The primary …

Role Of T Lymphocyte Trafficking In Diabetic Cardiomyopathy, Chowdhury Sayef Abdullah

Electronic Theses and Dissertations

Diabetic cardiomyopathy is a distinct pathological condition characterized by myocardial fibrosis and cardiac dysfunction in diabetic patients. The resolution of myocardial fibrosis to improve cardiac function in diabetes is an active area of research. Notably, increased T lymphocyte infiltration into myocardium has been attributed to increased cardiac fibrosis and dysfunction in diabetes. However, the experimental data on the role of T lymphocyte modulation in diabetic myocardial fibrosis is scarce. To this end, sphingosine 1-phosphate receptor 1 (S1P1) regulates the egress of mature T lymphocytes from lymphoid organs to blood and peripheral organs. Thus, the inhibition of T cells trafficking through …

Saffron Extract And Its Active Constituents As Preventative And/Or Treatment Agents For Prostate Cancer Using In Vitro And In Vivo Models, Faisal Fayih Albaqami

Electronic Theses and Dissertations

Saffron extract and its active constituents were evaluated as chemopreventatives and/or treatments for prostate cancer. Different models of prostate cancer (in vitro and in vivo) were used for studying saffron and its constituents’ mechanisms. In normal prostate cells, saffron extract, crocetin, and safranal, in non-toxic concentrations, possessed antioxidant properties against the reactive oxygen species induced by H2O2 which further supports saffron constituents as chemopreventative agents. Moreover, saffron and its active constituents produced cytotoxicity in prostate cancer cells through intrinsic apoptosis pathways. Potential efficacy in minimizing prostate cancer metastasis was also examined. Saffron extract, crocetin, and safranal decreased the migration and …

Evaluation And Enhancement Of Physical Stability Of Amorphous Solid Dispersions, Xin Feng

Electronic Theses and Dissertations

A major concern during formulation development has been to enhance the dissolution rate and bioavailability of poorly water-soluble drugs.[1],[2] The amorphous forms of APIs have attracted considerable attention as the amorphous forms tend to exhibit significantly higher levels of supersaturation in aqueous media when compared to the crystalline forms.[3],[4] For drugs which bioavailability is limited by aqueous solubility (biopharmaceutical classification system (BCS) class II drugs), which is a significant number of recently discovered drug candidates, the improved solubility may lead to enhanced bioavailability.[5-7] Oral absorption of APIs depends on two broad, but crucial, events, namely drug solubilization and gastrointestinal permeation.[8] …

Targeting Protein Kinases To Manage Or Prevent Alzheimer’S Disease, Manal A. Nael

Electronic Theses and Dissertations

Due to the pressing need for new disease-modifying drugs for Alzheimer’s disease (AD), new treatment strategies and alternative drug targets are currently being heavily researched. One such strategy is to modulate protein kinases such as cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase 5 (CDK5), glycogen synthase kinase-3 (GSK-3α and GSK-3β), and the protein kinase RNA-like endoplasmic reticulum kinase (PERK). AD intervention by reduction of amyloid beta (Aβ) levels is also possible through development of protein kinase C-epsilon (PKC-ϵ) activators to recover α-secretase levels and decrease toxic Aβ levels, thereby restoring synaptogenesis and cognitive function. In this way, we aim to develop …

Hot-Melt Extrusion: A Versatile Pharmaceutical Technology, Hemlata Patil

Electronic Theses and Dissertations

Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. The first objective of this research work was to describe a continuous process for the production of solid lipid nanoparticles (SLN) as drug-carrier systems via hot-melt extrusion (HME) using Quality by Design (QbD) principles. Fenofibrate SLN were prepared by combining two processes: HME technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. Varying the process parameters enabled the production of SLN below 200 nm. At the end of a 5-h in-vitro dissolution study, …