Pharmaceutics and Drug Design Commons^™

Design, Synthesis, And Evaluation Of A Novel Cytotoxic Peptide-Doxorubicin Conjugate Targeting Triple-Negative Breast Cancer, Elmira Ziaei

Pharmaceutical Sciences (PhD) Dissertations

The aim of this thesis was to design, synthesize, and characterize a novel peptide-doxorubicin conjugate, evaluate in vitro stability and cytotoxicity properties of the conjugate and study its mechanism for uptake into the triple-negative breast cancer (TNBC) cells. For the synthesis of the conjugate, first, doxorubicin (Dox) was conjugated to a highly efficient established cross-linker, MCC, to give an intermediate product, MCC-Dox. MCC-Dox was characterized using NMR spectroscopy, mass spectrometry, and RP-HPLC and purified for subsequent reaction. Second, the 11-mer peptide 18-4 (NH₂-CWxEAAYQrFL-CONH₂) with high proteolytic stability and specificity for breast cancer cells was reacted with …

Modulation Of Antibacterial Activity And Cytotoxicity In Amphipathic Cyclic Peptide [R4w4] Using Histidine Substitution, Ryan Stueber

Pharmaceutical Sciences (MS) Theses

Antibiotics have been the gold standard frontline defense against bacterial infections for decades. At the same time, these infecting bacteria have continued to evolve to resist developed antibiotics in an almost endless cycle. As such, we aim to take an alternative approach utilizing antimicrobial peptides (AMPs) as a means to end this cycle. [R4W4] is among known AMPs that demonstrated antimicrobial activity against methicillin-resistant staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 2.67 μg/mL. This peptide had notably effective antimicrobial activity, especially relative to linear (R4W4). However, it displayed a concerning level of cytotoxicity; eliciting a human embryonic …

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 …

Government As The First Investor In Biopharmaceutical Innovation: Evidence From New Drug Approvals 2010–2019, Ekaterina Galkina Cleary, Matthew J. Jackson, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

The discovery and development of new medicines classically involves a linear process of basic biomedical research to uncover potential targets for drug action, followed by applied, or translational, research to identify candidate products and establish their effectiveness and safety.

This Working Paper describes the public sector contribution to that process by tracing funding from the National Institutes of Health (NIH) related to published research on each of the 356 new drugs approved by the U.S. Food and Drug Administration from 2010-2019 as well as research on their 218 biological targets.

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

A Case Study Of Health Information System Workflow On Mitigating Opioid Drug Abuse In Saudi Arabia's Healthcare System, Alogaili Fahad Abdulrahman

Student Works (2020-2029)

The hospitals in Saudi Arabia, which have been studied in this research, are almost entirely automated. Healthcare information systems (HIS) are quite efficient; however, the health information exchange (HIE) is absent in the existing systems for different hospitals. Opioid drugs are an addictive substance, Saudi Arabia has the highest mean of drug abuse disorders in the region (680.5, group mean was 401.8). The lack of HIE had contributed significantly to the increase of opioid drug abuse in Saudi Arabia. If a patient has taken opioid as a painkiller, an interoperable system must have the information available for the healthcare department …

Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji

Pharmacy Faculty Articles and Research

Purpose: Ocular surface mucins and glycocalyx are critical for providing ocular hydration as well lubrication and repelling pathogens or allergens. Elevated levels of tear proinflammatory cytokines in dry eye may have detrimental effect on mucins and glycocalyx. The present study tested the effect of proinflammatory cytokines IL-6, TNF-α, and IFN-γ on membrane-tethered mucins expression, glycocalyx, and viability of ocular surface epithelial cells.

Methods: Stratified cultures of human corneal and conjunctival epithelial cells were exposed to different concentrations of IL-6, TNF-α, and IFN-γ for 24 hours. The mucins gene and protein expressions were quantified by real-time polymerase chain reaction …

Engineering And Characterization Of Human Β-Defensin-3 And Its Analogues And Microcin J25 Peptides Against Mannheimia Haemolytica And Bovine Neutrophils, Harpreet Dhingra, Kamaljit Kaur, Baljit Singh

Pharmacy Faculty Articles and Research

Mannheimia haemolytica-induced bovine respiratory disease causes loss of millions of dollars to Canadian cattle industry. Current antimicrobials are proving to be ineffective and leave residues in meat. Antimicrobial peptides (AMPs) may be effective against M. haemolytica while minimizing the risk of drug residues. Cationic AMPs can kill bacteria through interactions with the anionic bacterial membrane. Human β-Defensin 3 (HBD3) and microcin J25 (MccJ25) are AMPs with potent activity against many Gram-negative bacteria. We tested the microbicidal activity of wild-type HBD3, three HBD3 peptide analogues (28 amino acid, 20AA, and 10AA) derived from the sequence of natural HBD3, and MccJ25 …

Combating Hiv-1 By Targeting Drug Efflux Transporters On The Macrophage Reservoir, Ying Mu

Theses and Dissertations (ETD)

Introduction. HIV-1 eradication has not been achieved so far due to the existence of the cellular reservoir in which the virus can reside and replicate even under antiretroviral drug therapy (ART). Infected macrophages, which represent a long-term viral reservoir have been shown to lead to viral rebound independently. In response to the environmental stimuli, macrophages can be polarized into different phenotypes: the pro-inflammatory M1 and the anti-inflammatory M2. Tobacco smoking and alcohol drinking, which are prevalent among people who are living with HIV-1, have been shown to promote HIV-1 progression and decrease the efficacy of antiretroviral drugs. A commonly …

Modification And Antichlamydial Activity Evaluation On Dysregulators Of Cylindrical Proteases, Jiachen Feng

Theses & Dissertations

Chlamydia trachomatis infection is the most commonly reported sexually transmitted disease in the United States and the world. This pathogen can cause long-term health problems including blindness, pelvic inflammatory disease (PID) and ectopic pregnancy, which can be life-threatening if left untreated. To this day, there is no chlamydia-specific drug on the market. The standard treatment uses broad-spectrum antibiotics, which may affect regular functions of the commensal microbiota and leads to the development of bacterial resistance. Recently, a series of compounds based on Activators of Self-Compartmentalizing Proteases (ACP) was reported to show antichlamydial activity. Based on that scaffold, we prepared 21 …

Characterization Of Di-Aryl Urea Compounds Against Acute And Chronic Toxoplasma Gondii, Austin Sanford

Theses & Dissertations

Toxoplasma gondii is an obligate intracellular parasite that has infected nearly 60 million individuals in the United States alone. Acute infection causes ill effects to the fetus in utero when mothers are primarily infected, and to immunocompromised individuals. Chronic infection consists of quiescent tissue cysts located primarily in brain tissue and is capable of reverting back to the acute stage causing severe toxoplasma encephalitis in immunocompromised individuals. Current treatments for acute infection are lacking while there are no approved treatments for the clearance of chronic infection. The aim of this research was to evaluate a family of di-aryl urea compounds …

The Effects Of Dexmedetomidine On Preventing/Decreasing Severity Of Delirium When Given To Surgical Intensive Care Unit Patients: A Systematic Review Of Randomized Control Trials, Lindsey Hettish

The Eleanor Mann School of Nursing Undergraduate Honors Theses

The purpose of this systematic review was to integrate research evidence from studies published from 2010 to 2020 on the relationship between administration of dexmedetomidine and severity/prevalence of postprocedural delirium in patients in the surgical intensive care unit. In this review, clinical trial studies were recovered by searching the MEDLINE Complete and PubMed databases and utilizing MeSH terminology search. The MeSH terms utilized to search for applicable articles on PubMed included: “intensive care units” or “critical care” or “critical care nursing”, and “delirium”, “dexmedetomidine”, and “surgical procedures, operative”. On MEDLINE Complete, the search terms utilized were “ICU or intensive care …

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 …

Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Nayiri Alexander, Makena Augenstein, Angelina Sorensen, Matthew Gartner

Student Scholar Symposium Abstracts and Posters

Opioids such as morphine are important pain-relieving drugs but also carry a risk of harmful side effects including addiction. Morphine is active in both healthy and inflamed tissue, however, decreasing the pKa of the biochemically-active amine group can promote selective binding in the more acidic conditions of inflamed tissue and reduce harmful side effects associated with opioids. Herein, we explore the impact of fluorination on the pKa of fluoromorphine derivatives to identify which will bind selectively in inflamed tissue. Theoretical pKa values are determined at the M06-2X(SMD)/aug-cc-pVDZ level of theory to calculate the ΔGaq" …

Covid-19: The Vaccine Race Continues, L. Hayley Burgess, Carley Castelein, Andrew Rubio, Mandelin K. Cooper

HCA Healthcare Journal of Medicine

Over a year has passed since the discovery of SARS-CoV-2 and the subsequent COVID-19 pandemic. As mitigation efforts continue, COVID-19 has claimed over half a million lives in the United States and 3.1 million lives globally. The development and availability of vaccines delivering immunity to prevent COVID-19 offers hope to end the pandemic.

Emergency use authorizations from the Food and Drug Administration have been issued in the United States for three vaccines, one each from Pfizer-BioNTech, Moderna and Janssen/J&J. Pfizer-BioNTech and Moderna are both mRNA vaccines with efficacy of 95% and 94.1% respectively, while the vector-based vaccine from Janssen/J&J has …

Comprehensive In Silico Analysis Of Christinin Molecular Behaviour From Ziziphus Spina-Christi Leaves On Propionibacterium Acnes, Fitrianti Darusman, Taufik Muhammad Fakih

Pharmaceutical Sciences and Research

The role of in silico studies in the discovery of new drugs is very important and interesting in the recent years, where the results can be used as confirmation of the results of in vitro tests carried out experimentally in the laboratory. One of the herbal ingredients is Ziziphus spina-christi leaves with effective antibacterial activity, such as for acne-causing bacteria, namely Propionibacterium acnes. This is because it contains main secondary metabolites with saponins as the major components which contain christinin as its active compound. There are four known types of christinin, namely christinin-A, christinin-B, christinin-C, and christinin-D. In this …

Identification Of Adverse Drug Reactions In Congestive Heart Failure Patients In A Tertiary Care Hospital, West Nusa Tenggara, Indonesia, Dita Marina Lupitaningrum, Putri Ramdaniah, Depi Yuliana

Pharmaceutical Sciences and Research

Congestive Heart Failure (CHF) is a progressive health problem with high mortality and morbidity and has the potential to develop adverse drug reactions (ADRs). This study was conducted to determine the prevalence of potential ADRs, the types of drugs that cause ADRs, the types of ADRs, and the risk factors that affect the ADRs in CHF patients. Data were collected using medical record of hospitalized patient at the West Nusa Tenggara (NTB) Provincial Hospital, Indonesia, in 2017 to 2019. The assessment of the causality and severity of ADRs used the Naranjo algorithm and the Hartwig and Siegel scale. This study …

A Review: Composition Of Neonatal Meconium Microbiota And Its Role For Potential Probiotic, Devi Oktaviyani, Raden Zulfa 'Alawiyyah, Putri Nusaiba, Amarila Malik

Pharmaceutical Sciences and Research

Early-life period (≤ 1 month after birth) is critical for determining long- and short-term health of neonates. Composition of neonates’ gut microbiota varies greatly between individuals whose development is influenced by various factors including differences in maternal diet and lifestyle during pregnancy, related to population and ethnicity. Balanced microbial composition can create symbiosis among commensal microbes, immunomodulatory compound production, and subsequent immune response regulation. Unbalanced microbiota composition, characterized by more pathogenic organism, less diversity, and less resistance to disease, is called dysbiosis. Probiotic bacteria are a bacteria group contributing to the balance of neonates’ gut microbiota. Probiotic bacterial strains, such …

Interpersonal Relationship And Its Effect On Treatment Compliance In Patients With Type-2 Diabetes Mellitus, Fransiskus Samuel Renaldi, Woro Riyadina, Muhammad Qamar, Rani Sauriasari

Pharmaceutical Sciences and Research

Type-2 diabetes mellitus has become a chronic disease that can lead to serious complications and can only be prevented by compliant treatment of the patients. Compliance can be influenced by various factors, one of which is interpersonal factors. This study aimed to identify various interpersonal relationship problems between patients and healthcare workers that can affect their treatment compliance behavior. This study employed a qualitative design with phenomenological methods. This research was conducted in Central Bogor City in March-August 2020. The data were collected by conducting in-depth interviews with 20 type-2 diabetes mellitus patients who had been confirmed by the Community …

Drug Repurposing And Dosage Form Development Of Anti-Covid-19, Kevin Kwok

Pharmaceutical Sciences and Research

The COVID-19 pandemic has been occurring approximately for more than 1 year. This pandemic has been a health issue that hits all countries in the world caused by the transmission of SARS-CoV-2 virus from one individual to another. The symptoms showed from the infected are fever, shortness of breath, dry cough, headache, and sore throat, among others. The SARS-CoV-2 virus is transmitted through sneezing, coughing, talking, and touching infected objects. Along with this transmission, the SARS-CoV-2 virus will continue to mutate. This mutation becomes an obstacle as well as a challenge to find drugs that can overcome the SARS-CoV-2 virus …