Pharmaceutics and Drug Design Commons^™

Association Of Environmental Pollutants Exposure With Pulmonary Fibrosis: A Mini Review Of Molecular Mechanism Mediated, Soni Siswanto, Bantari W.K. Wardhani

Pharmaceutical Sciences and Research

Pulmonary fibrosis is a specific form of chronic progressive interstitial lung disease. Deposition of extracellular matrix, mainly collagen, is the pathogenic characteristic of pulmonary fibrosis. Many reports show that environmental pollutants, particularly asbestos, silica, mercury, cadmium, and benzo(a)pyrene, are contributed in the etiology of lung injury and a risk factor in the development of idiopathic pulmonary fibrosis (IPF) in humans. Based on its physicochemical properties, environmental pollutant-induced pulmonary fibrosis can be developed after a particular type or dose of exposure. To date, some studies have focused on variant pollutants that are induced. However, the molecular mechanism of various pollutants to …

Antihypertensive And Antioxidant Activity Of Herbal Medicine (Jamu) B On Rats Induced By 10% Fructose, Aprilita Rina Yanti Eff, Reza Ayu Pertiwi, Hermanus Ehe Hurit, Sri Teguh Rahayu, Yonatan Eden

Pharmaceutical Sciences and Research

Prolonged fructose intake can activate the renin-angiotensin-aldosterone system and enhance oxidative stress conditions, causing hypertension and hyperuricemia. This study aimed to determine the antihypertensive and antioxidant activity of Jamu B on the activity of superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the kidneys of Sprague Dawley rats induced by 10% fructose. Thirty rats were divided into six groups. Groups B1-B3 were Jamu groups at a dose of 0.12 g/kg BW (B1), 0.24 g/kg BW (B2), and 0.36 g/kg BW (B3); group C (positive control) was given captopril 0.1 g/kg BW, group D (negative control) was given only 10% …

Oleyl Conjugated Histidine-Arginine Cell-Penetrating Peptides As Promising Agents For Sirna Delivery, Muhammad Imran Sajid, Dindyal Mandal, Naglaa Salem El-Sayed, Sandeep Lohan, Jonathan Moreno, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Recent approvals of siRNA-based products motivated the scientific community to explore siRNA as a treatment option for several intractable ailments, especially cancer. The success of approved siRNA therapy requires a suitable and safer drug delivery agent. Herein, we report a series of oleyl conjugated histidine–arginine peptides as a promising nonviral siRNA delivery tool. The conjugated peptides were found to bind with the siRNA at N/P ratio ≥ 2 and demonstrated complete protection for the siRNA from early enzymatic degradation at N/P ratio ≥ 20. Oleyl-conjugated peptide -siRNA complexes were found to be noncytotoxic in breast cancer cells (MCF-7 and MDA-MB-231) …

Acetaminophen, A Therapeutic Or An Extremely Toxic Remedy – A Review, Genica Caragea, Oana Avram, Andreea Pauna, Andreea Cristina Costea, Miruna Tudosie

Journal of Mind and Medical Sciences

When a new coronavirus appeared in the late 2019, identified as the cause of several cases of pneumonia in Wuhan, Paracetamol was initially reported to be the preferable antipyretic medication, choice which was detrimental to the use of other drugs. People have resorted to buying large stocks of Paracetamol and some have used it in large doses, regardless of the consequences. However, the Paracetamol (Acetaminophen) overdose remains the leading cause of death or transplantation due to acute liver failure in many parts of the world. This review aims at presenting the pharmacokinetics, the clinical signs, and the risk factors for …

The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen

CSB and SJU Distinguished Thesis

An unexpected outbreak of SARS-CoV-2 caused a worldwide pandemic in 2020. Many repurposed drugs were tested, but there are currently only three FDA approved antivirals (Merck’s antiviral Molnupiravir, Pfizer’s antiviral Paxlovid, and Remdisivir).1 Most of the antiviral drugs tested SARS-CoV-2 main protease and RNA-dependent RNA polymerase. However, it is important to explore different drug targets of SARS-CoV-2 to prepare for the virus mutations of the future. This research looks at an alternative approach in which SARSCoV- 2 Open Reading Frame 8 (ORF8), which has been shown to be a rapidly evolving hypervariable gene, was chosen to be the protein of …

Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen

CSB and SJU Distinguished Thesis

Severe acute respiratory syndrome (SARS-CoV-2) led to the COVID-19 global pandemic, with over 460 million cases of infection and over 6 million deaths since the start of the pandemic. SARS-CoV-2 is a retrovirus that utilizes a main protease (Mpro). Mpro is a catalytic cys/his protease. Several treatments were proposed to stop the pandemic including repurposing drugs to inhibit the Mpro. Another retrovirus that uses a protease is human immunodeficiency virus (HIV-1) which has been a global epidemic for 40 years and is a devastating disease that attacks the immune system. HIV-1 has infected 79.5 million people and has killed an …

A Proposed Treatment Of Mixed Connective Tissue Disease By Competitive Inhibition Of Autoantibodies, Thomas Russell

Senior Honors Theses

Mixed Connective Tissue Disease is an autoimmune disease characterized by Raynaud’s phenomenon and arthritis among other symptoms. It is primarily caused by antibodies that target the U1-RNP 70K peptide. The treatment proposed in this paper uses competitive inhibition to prevent the binding of the anti-U1-RNP 70K antibodies with the U1-RNP 70K peptide. A method for testing the designed treatment in silico is proposed using AutoDock Vina docking software.

Evaluation Of Protective Efficacy Of Viral Vector Based Swine Influenza Vaccine And A Method For B Cell Culture For Monoclonal Antibody Generation, Sushmita Kumari

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

Influenza A virus of the swine (IAV-S) is an economically important swine pathogen that has the potential to spread to humans, thus posing an ongoing public health concern due to its zoonotic potential. Hemagglutinin (HA), the most abundant viral envelope protein, is known to be the key protective antigen. Anti-HA antibodies alone, have been shown to prevent IAV infection. In this study we evaluated the feasibility of a recombinant tri segmented Pichinde virus (PICV) as a viral vector to deliver IAV-S hemagglutinin antigen in pigs. Four groups of weaned pigs (T01-04) were immunized twice with PBS, rPICV-GFP as a vector …

Targeting Protein Degradation To Uncover Novel Oncoprotein Drivers Of Acute Leukemia, Fatemeh Keramatnia

Theses and Dissertations (ETD)

Acute Lymphoblastic Leukemia (ALL), the most common childhood cancer and the second most common acute leukemia in adults, arises from clonal expansion of undifferentiated lymphoid precursor cells in bone marrow. Despite the extensive knowledge on its cytogenetic and molecular biology, ALL treatment remains highly challenging especially after relapse. Conventional chemotherapy has shown significant improvement in overall survival rates of pediatric patients up to 90%, however, treatment failure due to ALL relapse occurs in 15-20% of the cases. On the other hand, adults and elderly patients with ALL are considered difficult to treat populations with the 5-year overall survival of 30–40%. …

Chloroquine-Susceptible And -Resistant Plasmodium Falciparum Strains Survive High Chloroquine Concentrations By Becoming Dormant But Are Eliminated By Prolonged Exposure, Johan Ursing, Rasmus Johns, Berit Aydin-Schmidt, Carla Calçada, Poul-Erik Kofoed, Najia Karim Ghanchi, Maria Isabel Veiga, Lars Rombo

Department of Pathology and Laboratory Medicine

Background: Plasmodium falciparum strains that are resistant to standard-dose chloroquine can be treated by higher chloroquine concentrations maintained for a longer time in vivo.
Objectives: To determine the relative importance of chloroquine concentrations versus exposure time for elimination of chloroquine-susceptible and -resistant P. falciparum in vitro.
Methods: Chloroquine-susceptible (3D7) and -resistant (FCR3) strains were exposed in vitro to 1, 2, 4, 8, 16 or 32 times their respective 90% inhibitory chloroquine concentrations for 3, 5, 7 or 14 days and then followed until recrudescence, or not, by 42 days after the end of exposure.
Results: Exposure to chloroquine appeared to …

An Evaluation Of The Effect Of The Oxycontin® Reformulation On Unintentional Fatal And Non-Fatal Overdose, Daniel C. Beachler, Kelsey Hall, Renu Garg, Geetanjoli Banerjee, Ling Li, Luke Boulanger, Huseyin Yuce, Alexander M. Walker

Publications and Research

Objectives: OxyContin® was reformulated with a polyethylene oxide matrix in August 2010 to reduce the potential for intravenous abuse and for abuse by insufflation. The objective of this study was to evaluate the impact of OxyContin’s reformulation on overdose risk for individuals dispensed OxyContin in comparison to those dispensed other opioids under regular care. Methods: Three national insurance databases with National Death Index linkage identified OD in individuals with any dispensing of OxyContin or a primary comparator opioid (ER morphine, transdermal fentanyl, or methadone) between July 2008 through September 2015. A difference-in-differences design was used to compare the pre-post reformulation …

Comparison Of Liposomal Bupivacaine Versus Bupivacaine With Epinephrine Versus The Combination In Postoperative Pain Management Following Spinal Surgery, Arianne Dagdag

Annual Research Symposium

No abstract provided.

Emerging Drug Targets And New Drugs In The Treatment Of Psoriatic Arthritis, Carmen Lariccia, Natalie Lennartz, Jessica Lewe, Jeffery Allison

Pharmacy and Wellness Review

Psoriasis is an autoimmune disease characterized by painful skin lesions. When joints and connective tissue also become involved, the condition is referred to as psoriatic arthritis (PsA). Current treatments for moderate to severe PsA include therapies used to treat rheumatoid arthritis (RA) despite differences in disease presentation which includes factors such as peripheral disease, sacroiliitis, stiffness, presence of rheumatoid factor and psoriasis. Treatment out-comes for PsA are measured by the American College of Rheumatology (ACR) Responder Index (ACR20) and the Dis-ease Activity Score for 28 joints (DAS28). First-line treatment includes disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, sulfasalazine or leflunomide …

Management Of Hyperkalemia To Prevent Cardiac Arrest, Jennifer Harklerode, Amber Paul, Crystal Zheng, Olivia Vanscoy, Olivia Henton, Mark Olah

Pharmacy and Wellness Review

Hyperkalemia is a metabolic problem that may be life threatening if left untreated. Cardiac arrhythmias may develop with the potential to lead to cardiac arrest and death. Hyperkalemia can oftentimes be undiagnosed due to the lack of clear, specific symptoms and inconclusive variations in electrocardiogram (ECG) readings and lab values. Therefore, it is important to recognize risk factors that can potentially in-crease serum potassium levels. Screening for medications that increase serum potassium levels and educating patients are steps that both inpatient and outpatient health care professionals can take to increase early detection and prevention of a hyperkalemic episode. It is …

Daclizumab (Zinbryta®): An Emerging Therapy For The Treatment Of Relapsing-Remitting Multiple Sclerosis, Morgan Homan, Sunitha Jones, Michaela Louden, Molly Wheeler, Anh Dao Le, Lindsey Peters

Pharmacy and Wellness Review

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system characterized by the deterioration of the myelin sheath, causing axonal damage which leads to debilitating symptoms. Most therapies for the treatment of MS, including daclizumab, primarily target relapsing-remitting multiple sclerosis (RRMS), a form of MS where patients experience periods of exacerbated symptoms as well as intermittent periods of remission. Daclizumab is a humanized monoclonal antibody that is administered as a once monthly subcutaneous injection. The SELECT trilogy of trials have been instrumental in providing safety and efficacy data for daclizumab. The DECIDE study was the first randomized controlled …

Lipid Based Nanoparticles As A Novel Treatment Modality For Hepatocellular Carcinoma: A Comprehensive Review On Targeting And Recent Advances, Khaled Mahmoud, Shady Swidan, Mohamed A. El-Nabarawi, Mahmoud H. Teaima

Pharmacy

Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles—specifically lipid based nanoparticles—are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, …

Variants Associated With Bedaquiline (Bdq) Resistance Identified In Rv0678 And Efflux Pump Genes In Mycobacterium Tuberculosis Isolates From Bdq Naïve Tb Patients In Pakistan, Dania Khalid Saeed, Sadia Shakoor, Safina Abdul Razzak, Zahra Hasan, Saba Faraz Sabzwari, Zahida Azizullah, Akber Kanji, Asghar Nasir, Samreen Shafiq, Najia Karim Ghanchi, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: Mutations in the Rv0678, pepQ and atpE genes of Mycobacterium tuberculosis (MTB) have been reported to be associated with reduced antimycobacterial susceptibility to bedaquiline (BDQ). Resistance conferring mutations in treatment naïve MTB strains is likely to have implications for BDQ based new drug regimen that aim to shorten treatment duration. We therefore investigated the genetic basis of resistance to BDQ in MTB clinical isolates from BDQ naïve TB patients from Pakistan. In addition, mutations in genes associated with efflux pumps were investigated as an alternate mechanism of resistance.
Methods: Based on convenience sampling, we studied 48 MTB clinical isolates …

The Use Of Advanced Spectral Imaging To Reveal Nanoparticle Identity In Biological Samples, Qamar A. Alshammari, Rajasekharreddy Pala, Ayan K. Barui, Saud O. Alshammari, Andromeda M. Nauli, Nir Katzir, Ashraf M. Mohieldin, Surya M. Nauli

Pharmacy Faculty Articles and Research

Nanoparticles (NPs) have been used in drug delivery therapies, medical diagnostic strategies, and as current Covid-19 vaccine carriers. Many microscope-based imaging systems have been introduced to facilitate detection and visualization of NPs. Unfortunately, none can differentiate the core and the shell of NPs. Spectral imaging has been used to distinguish a drug molecule and its metabolite. We have recently integrated this technology to a resolution of 9 nm by using artificial intelligence-driven analyses. Such a resolution allowed us to collect many robust datapoints for each pixel of an image. Our analyses could recognize 45 spectral points within a pixel to …

Three Waves: The United States Opioid Crisis, Ryan B. Santoro

Senior Scholars Papers in Science, Technology, and Society

The past two and a half decades have witnessed widespread suffering, addiction, and death at the hands of the opioid crisis. This paper analyzes the crisis through a series of time periods, broken down into “waves.” Drawing upon primary material in relation to OxyContin advertisements in the 1990’s, this research takes aim at the origin of widespread opioid abuse disorder. By building upon analysis done on the Sackler Family, Purdue Pharma, heroin abuse, fentanyl overdoses, the COVID-19 pandemic and opioids and addiction in modern pop culture, this thesis shows how despite constant change in public policy, the opioid crisis continues …

The Water Solubility Of Ursolic Acid Complexes At Different Choline Concentrations, Sera Lim, Renjie Zhan, Phillip M. Gerk

UROP Posters

No abstract provided.

Modified Ysk12-Mend-Sirna In Dendritic Cells For Cancer Immunotherapy, Syed S. Alam

UROP Posters

Tumors may induce tolerogenesis through signaling dendritic cells to produce tolerogenic molecules, such as indoleamine 2, 3-dioxygenase 1 (IDO1). Tumor-associated immunosuppression is associated with higher mortality in patients. Small interfering RNA (siRNA) has been shown to silence specific target genes in the target cell. The siRNA associated with these genes could support a gene knockdown of these immunosuppressors and reduce mortality. Delivery of these therapeutic nucleic acids is difficult in vivo because siRNA is easily broken down inside the cell and the bloodstream through present nucleases. Use of liposome polymers has been reviewed extensively in literature. YSK12-C4, a lipid nanoparticle …

Putative Mechanisms Underlying The Antidepressant Actions Of Ketamine: A Review And Study Proposal, Tristan Reece

CMC Senior Theses

Major Depressive Disorder (MDD) is a highly debilitating and common psychiatric disorder that affects over 250 million people globally; it is among the most financially and emotionally burdensome illnesses in the world. Currently approved antidepressants are suboptimal in their efficacy and latency of therapeutic action. In contrast, single administrations of sub-anesthetic ketamine have been shown to rapidly alleviate depressive symptoms within hours, even in treatment-resistant patients. Ketamine is believed to exert these effects by increasing glutamatemediated neurotransmission and promoting rapid neurotrophic factor release, restoring the integrity of neural circuits that are compromised in depression. However, uncertainty surrounding its specific antidepressant …

Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck

Theses and Dissertations--Pharmacy

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.

The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABA_A receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABA_A receptor interaction suggests that …

Studies Toward The Development Of An Improved Countermeasure For Synthetic Opioid Overdose, Sidnee L. Hedrick

Theses and Dissertations--Pharmacy

One of the most prominent opioid analgesics in the United States is the high potency agonist fentanyl. It is used in the treatment of acute and chronic pain and as an anesthetic adjuvant. When used inappropriately, however, ingestion of just a few milligrams of fentanyl or other synthetic opioid can cause opioid-induced respiratory depression (OIRD), often leading to death. Currently, the treatment of choice for OIRD is the opioid receptor antagonist naloxone. Recent reports, however, suggest that higher doses or repeated dosing of naloxone (due to recurrence of respiratory depression) may be required to fully reverse fentanyl-induced respiratory depression, rendering …

Investigating The Physical Stability Of Amorphous Pharmaceutical Formulations, Travis W. Jarrells

Theses and Dissertations--Pharmacy

Amorphous formulations, including amorphous solid dispersions (ASDs), consisting of the active pharmaceutical ingredient (API) intimately mixed in a polymeric matrix, are an attractive formulation approach to improve drug delivery, dissolution, and solubility. However, an amorphous API in an ASD is in a higher energy state compared to the crystalline drug and results in most ASDs being inherently unstable. The polymer helps to stabilize the amorphous drug against crystallization such that the resulting homogenous mixture maintains its solubility advantage relative to the crystalline form. One challenge of ASDs is that the presence of impurities including crystals or residual solvent, variations in …

Response Of Dopaminergic System To Cocaine Exposure, Recovery After Cocaine Abstinence, And Impact Of A Long-Acting Cocaine Hydrolase, Jing Deng

Theses and Dissertations--Pharmacy

Cocaine produces its physiological effects by targeting multiple proteins in the central nervous system, particularly by binding with dopamine transporter (DAT) to block the normal dopamine (DA) recycling process. This process along with the pleasure feeling would wear off shortly after the abstinence from the drug. However, chronic cocaine use is associated with neuroadaptations in the dopaminergic system, including increases in the density of DAT on plasma membrane of dopaminergic neurons. Given the critical role of DAT in neurotransmission, various studies have been carried out on animal models to learn its structure, function, and distribution. Long-standing evidence supports that DAT …

Liposomal Technologies To Improve Gene Delivery, David Nardo Padron

Theses and Dissertations--Pharmacy

Lipid based nanoparticles (LBNs) are used in myriad applications in medicine from small molecule drug delivery to mRNA vaccines. A major contributing factor to the development of the field has been the ongoing development of novel compounds that retain the functionality of natural lipids but expand upon them through inclusion of functional moieties that can be applied to specific scientific and biomedical questions. In the body of this dissertation, an extensive overview of LBNs is provided, focusing primarily on their use in immune modulation. The research presented herein begins with the synthesis of a novel class of lipids based on …

Development Of Accurate And Efficient Computational Methodologies For Predicting Protein-Ligand And Protein-Protein Binding Free Energies, Alexander Hamilton Williams

Theses and Dissertations--Pharmacy

Computational modeling is an invaluable tool in the drug discovery process either for small ligand or protein therapeutics. The widespread availability of protein X-Ray Crystal and Cryo-Electron Microscopy (Cryo-EM) structures has allowed for more accurate molecular dynamics (MD) simulations that are not reliant on methods such as homology modeling, which may produce structures that require significant computational time to demonstrate their stability. In this thesis we describe several novel methodologies for the computationally efficient modeling of protein/ligand and protein/protein complexes that may be employed within both large-scale virtual screenings and lead compound optimization. These methodologies may also be utilized in …

Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala

Graduate Theses, Dissertations, and Problem Reports (ETD)

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …

Ero1Α Promotes Tumorigenesis In Egfr Driven Nsclc, Brennan D. Johnson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-Small Cell Lung Cancer (NSCLC) is a pulmonary malignancy most commonly associated with smoking, or exposure to asbestos or Radon. Approximately, 1.6 Million deaths occur each year due to lung cancer. Lung Cancer is categorized by two main types, Small Cell Lung Cancer (SCLC) and NSCLC. NSCLC accounts for approximately 85% of all lung cancer cases and is subdivided into three sub-categories: Adenocarcinoma, the most common and leading cause of death in the United States; Squamous Cell Carcinoma (SCC), and Large Cell Carcinoma. Though NSCLC treatment regimens have shown increasing clinical benefit over the last two decades with targeted therapies. …