Chemicals and Drugs Commons^™

Understanding The Impact Of Solvents In Oral Solid Dosage Formulation And Process Development, Matthew Kyle Defrese

Theses and Dissertations--Pharmacy

The successful delivery of chemical compounds for the purpose of therapeutic treatments and prophylactics is a substantial undertaking in modern drug development. Notably, the adoption of high throughput screening techniques has led to the proliferation of poorly water soluble and/or highly potent molecules which further complicate development activities. Spray dried amorphous solid dispersions are an increasingly important formulation strategy to overcome solubility issues while wet granulation approaches are the method of choice for the preparation of highly potent APIs in oral solid dosage forms.

A common connection between these critical techniques is their reliance on solvent-based processing that can often …

Investigation Of The Biosynthesis Of The Nucleoside Antibiotic Sphaerimicin, Jonathan Overbay

Theses and Dissertations--Pharmacy

Antibiotic-resistance has become a widespread problem in the United States and across the globe. Meanwhile, new antibiotics are entering the clinic at an alarmingly low rate. Highly-modified nucleosides, a class of natural products often produced by actinobacteria, target MraY bacterial translocase I. MraY is a clinically unexploited enzyme target that is ubiquitous and essential to peptidoglycan cell wall biosynthesis. The nucleoside antibiotics known vary in efficacy and the functionalities contributing to improved activity is poorly understood. Sphaerimicin, a newly discovered modified nucleoside, has potent inhibitory activity with an IC50 of 13.65 nM against MraY. In general, sphaerimicin is primarily effective …

Additive Manufacturing In Personalized Medicine: Patient-Customized Solid Dose Medicines, And Patient-Customized Wound Care Device, Amir Najarzadeh

Theses and Dissertations--Mechanical and Aerospace Engineering

Personalized Medicine - from a one-size fits all to a tailored approach is the future in pharmaceutical therapeutics and medical applications. The aim of this study is demonstrate additive manufacturing in two personalized medicine applications: 1. Patient- customized solid dose medicines, and 2. Patient-customized wound care device. The aim of the first application is to develop an inexpensive and accurate method to design and fabricate patient-customized tablets. Particularly this paper focuses on fabricating and dose controlling of patient-customized extended release prednisolone-poly(vinyle alcohole) PVA. Dry-Blending, Wet Granulation, Extrusion, Spherionization, Hot melt extrusion (HME) was adopted to produce drug loaded prednisolone-PVA filaments …

Therapeutic Drug Monitoring Of Beta-Lactam Antibiotics In Critically Ill Patients With Sepsis, Melissa Thompson Bastin

Theses and Dissertations--Clinical and Translational Science

Sepsis is a devastating diagnosis affecting over 750,000 patients a year, accounting for approximately 10% of all hospital admissions, costs more than $50,000 per patient, and exceeds $17 billion annual spending. The mortality rate for sepsis remains unacceptably high: one out of every three patients diagnosed with sepsis dies. Sepsis physiology induces physiologic changes to drug pharmacokinetic (PK) parameters that alter the ability to achieve the goal pharmacodynamic (PD) target for beta-lactams of >4-fold unbound concentration above the minimum inhibitory concentration for 100% of the dosing interval (100% fT >4x MIC). Sepsis treatment such as volume resuscitation and vasopressor …

The Gestation Of Health: Environmental Insults, Behavioral Interventions, And Protective Mechanisms, Brittany Breon Rice

Theses and Dissertations--Pharmacology and Nutritional Sciences

Diabetes remains a leading cause of death nationwide despite pharmacological advances. Recent etiological investigations of the disease detail the role of perinatal exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), in enhancing disease susceptibility. Polychlorinated biphenyl 126, a coplanar PCB, elicits its toxic effects through the aryl-hydrocarbon receptor and the disruption of endocrine signaling. The goal of this dissertation was to focus on delineating the differences in the developmental windows of diabetes susceptibility respective to the timing of PCB126 exposure and to understand the influence of maternal exercise and nuclear-factor erythroid-2-related factor 2 (Nrf2) expression in combating the negative …

Base-Labile Protecting Groups For Stepwise Peg Synthesis, Logan D. Mikesell

Dissertations, Master's Theses and Master's Reports

Stepwise synthesis of monodisperse polyethylene glycols (PEGs) and their derivatives usually involves using an acid-labile protecting group such as DMTr and coupling two PEG moieties together under the basic Williamson ether formation conditions. Using this approach, each elongation of PEG is achieved in three steps – deprotection, deprotonation, and coupling – in two pots. Here, we report a more convenient approach for PEG synthesis featuring the use of a base-labile protecting group such as the phenethyl group. Using this approach, each elongation of PEG can be achieved in only two steps – deprotection and coupling – in one pot. The …

Actividades Profesionales Reservadas En Argentina: Orígenes Y Actualidad / Reserved Professional Activities In Argentina: Origins And Current Situation, Cintia E. Citterio, Héctor Targovnik

Pharmacy Faculty Articles and Research

En Argentina, la Ley de Educación Superior (LES; Ley 24.521, 1995) establece que hay profesiones cuyo ejercicio puede comprometer el interés público poniendo en riesgo de modo directo la salud, la seguridad, los derechos, los bienes o la formación de los habitantes, y las mismas están contempladas en el artículo 43 de la LES. Sólo aquellas actividades que realicen estos profesionales y que implican un riesgo rigurosamente directo, se denominan actividades profesionales reservadas. Pero… ¿Cuál es la diferencia entre actividades profesionales reservadas y alcances de los títulos? ¿Y cómo se establecen? El objetivo de este trabajo es analizar el significado …

'Induction Of Apoptosis, Cytotoxicity And Radiosensitization By Novel 3,4-Dihydroquinazolinone Derivatives, Eman Ramadan, Amira Khalil

Pharmacy

Twenty new quinazolinone derivatives bearing a piperonyl moiety were designed and synthesized. The structures of the target compounds were in agreement with the microanalytical and spectral data. Compounds 4-10, 13, 14 and 17-27 were screened for their cytotoxic activity against HepG-2 and MCF-7 cancer cell lines. The target compounds showed IC₅₀ in the range of 2.46-36.85 µM and 3.87-88.93 µM for HepG-2 and MCF-7, respectively. The promising compounds 7, 19, 26 and 27 were selected to measure their EGFR inhibitory activity. The IC₅₀ values of the promising compounds were in the range of 146.9-1032.7 nM for EGFR in …

Sansevieria: An Evaluation Of Potential Cytotoxic Activity In Reference To Metabolomic And Molecular Docking Studies, Amgad Albohy

Pharmacy

Sansevieria trifasciata Prain. and Sansevieria suffruticosa N.E.Br. were selected to evaluate their cytotoxic activity against colon (CACO2), lung (A-549) and liver (HepG-2) carcinoma cell lines. Results indicated that S. suffruticosa N.E.Br. showed a significant cytotoxic effect on CACO2 with IC50= 30.9 ± 0.72 μg/ml. Evaluating the phenolic and flavonoid contents, S. suffruticosa N.E.Br. has higher total phenolic and flavonoid contents than S. trifasciata Prain. The phenolic content was estimated using HPLC detecting the presence of apigenin-7-glucoside and cinnamic acid only in S. suffruticosa N.E.Br. with p-hydroxybenzoic acid and p-coumaric acid being the major compounds. While, catechin and kaempferol are the …

Neuroprotective Repositioning And Anti-Tau Effect Of Carvedilol On Rotenone Induced Neurotoxicity In Rats: Insig& In Vivo Anti-Parkinson’S Disease Studyhts From An Insilico, Amgad Albohy, Rana Kamal, Esther Menze, Hebatalla I. Ahmed, Samar S. Azab

Pharmacy

Current treatments for Parkinson’s Disease (PD) only provide symptomatic relief; however, they don’t delay the disease progression, hence new treatment options should be considered. Carvedilol is a nonselective β & α1 blocker with additional effects as an antioxidant, anti-inflammatory and neuro protective properties. In this research, an insilico study was conducted to primarily evaluate carvedilol as an anti-parkinsonian and anti-tau protein target. PASS prediction was performed followed by a docking study of carvedilol. Carvedilol yielded promising results and forward guided this study onto its in vivo evaluation. The in vivo study aimed to assess the neuro-protective effects of carvedilol in …

Philippine Medicinal Plants With Potential Immunomodulatory And Anti-Sars-Cov-2 Activities, Fabian M. Dayrit, Armando M. Guidote Jr, Nina Gloriani, Sheriah Laine M. De Paz-Silava, Irene M. Villaseñor, Rene Angelo S. Macahig, Mario A. Tan, John Ross N. Chua, Isidro C. Sia

Chemistry Faculty Publications

Coronavirus disease 2019 (COVID-19) continues to devastate the world’s health and economy, affecting all aspects of life leading to widespread social disruption. Even as several vaccines have been developed, their availability in developing countries is limited and their efficacy against the variants of SARS-CoV-2 (severe acute respiratory syndrome–coronavirus 2) needs to be continuously assessed. The World Health Organization (WHO) has acknowledged that vaccines alone will not overcome the global challenges of COVID-19. Medicinal plants may provide the needed support. Herein, we identify Philippine medicinal plants that possess phytochemicals with potential anti-SARS-CoV-2 activity and/or immunomodulatory properties that may strengthen one’s immune …

New Dithiocarbamates As A Possible Human Serum Albumin Metal Carrier In Drug Delivery Systems And Their Antioxidant And Antiproliferative Activities, Saadi M.D. Al-Nuzal, Azhar M. Haleem, Ken Czerwinski, Salah M. Haleem

Chemistry and Biochemistry Faculty Research

New mono- and bis-dithiocarbamates were prepared from the reaction of organic dihydrazides -NHNH-(C=O)(CH2)x-(C=O)NHNH- (where x = 0, 2, 4) and basic carbon disulfide with varying chain length 10-14 atom as a human serum metal carrier. The products were characterized by various spectrophotometric such as 1H and 13C NMR and elemental analysis. Their antiproliferative activities were examined on two species of the standard strains of the Gram-positive Staphylococcus aureus ATCC 25923 and Gram-negative Escherichia coli ATCC 25922 by following the procedure of broth micro-dilution method (BMM), which was applied at the concentrations: 0.0, 100, 200, and 300 ppm for each compound. …

Risk Factors And Trends In Antimicrobial Susceptibility Patterns In Strains Of Neisseria Gonorrhoeae Following Changes In The Cdc Sexually Transmitted Disease (Std) Treatment Guidelines – United States, 2012-2018, Niketta A. Womack

College of Graduate Studies: Theses & Dissertations

Antimicrobial resistant Neisseria gonorrhoeae (N. gonorrhoeae) has become a major global public health concern in the 21st century. Surveillance activities are essential in identifying risk factors in priority populations. The purpose of this study was to identify risk factors associated with and trends in antimicrobial susceptibility patterns in N. gonorrhoeae strains identified through the Gonococcal Isolate Surveillance Project (GISP). A study sample of 37,157 men was evaluated to measure adherence to changes in CDC’s STD treatment guidelines in 2012 and 2015. Data were analyzed to measure associations between independent and dependent variables by conducting bivariate and logistic regression …

The Role Of Cannabidiol In The Treatment Of Pediatric Patients With Refractory Epilepsy, Evan Chidley

Capstone Showcase

THE ROLE OF CANNABIDIOL IN THE TREATMENT OF PEDIATRIC PATIENTS WITH REFRACTORY EPILEPSY

Author(s) and affiliations: Evan Chidley¹, MMS (c), MPH (c)

¹Arcadia University; [email protected]; (515) 201-6901

Introduction: Intractable epilepsy in children can significantly impair quality of life and anti-epileptic drugs (AEDs) do not adequately reduce seizures for all pediatric patients. Recently, cannabidiol (CBD), one of the main compounds of marijuana, has shown promise as a potential treatment for uncontrolled seizure activity. This paper poses the following question: In pediatric patients with drug-resistant epilepsy, is cannabidiol (CBD) more effective in reducing seizure activity than traditional anti-epileptic drugs …

Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori

Capstone Showcase

Opioid Use Disorder is patterns of opioid use leading to withdrawal, giving up important life events in order to use opioids, and excessive time spent using opioids, to name a few diagnostic criteria. The clinical progression of the disorder involves periods of acute exacerbation and remission that are cyclic in nature. Treatment is most effective when it includes both pharmacological and psychosocial modalities, referred to as medication assisted therapy (MAT). Three drugs used commonly in MAT-based treatment for OUD from oldest to newest include Methadone, Buprenorphine-naloxone, and Naltrexone. Treatment program models that prioritize total abstinence from the addictive substance attached …

Naloxone/Buprenorphine, Methadone, Naltrexone And Their Role In Medication Assisted Treatment, Robert Barrett

Capstone Showcase

Abstract

Opioid use disorder (OUD) is an increasingly common diagnosis that has drastically increased in the last 5 years. Though multiple treatment modalities exist for treating OUD (naltrexone, buprenorphine, methadone), few studies have compared treatment outcomes in adults on long term therapy. This is an important topic to understand as providers as we will undoubtedly come into contact with patients either actively abusing opioid antagonists or in recovery from opioid abuse. Since the introduction of Oxycontin and subsequent over prescription of opioid analgesics, opioid overdoses have increased by over twelve-fold. Once providers began to realize a widespread pattern of abuse, …

How The Amino Acid L-Serine Provides Neuroprotection Against L-Bmaa Induced Alzheimer’S Disease, Joseph Cimino

Capstone Showcase

More than 6 million people in America are living with Alzheimer’s Disease (AD) and there are currently no cures or treatments. It is time to move on from the ꞵ-amyloid hypothesis and broaden AD research. New research is suggesting that dietary exposure to a cyanobacterial toxin known as L-BMAA is causing neurodegenerative diseases such as AD, Amyotrophic lateral sclerosis (ALS), and Parkinson’s Disease. L-BMAA is misincorporated during protein folding, in place of the proper amino acid, L-Serine. It has been shown that the naturally occurring amino acid, L-Serine, can provide neuroprotection against L-BMAA, but the mechanism by which L-Serine infers …

Therapeutical Studies Of The Disrupted Cftr Gene In Affected Sheep And Rabbit Models Produced By Genome Editor Crispr/Cas9, Nicole Teberio

Capstone Showcase

Cystic Fibrosis (CF) is a life-threatening, autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Patients with CF have a decreased lifespan due to complications with lung infections/disease, decreased airway function, and persistent cough with phlegm. Over the past few decades, scientists have contributed to CF research by using animal models to understand the pathology of the disease. The models selected have similar pathogenesis to humans, so they are key insights for understanding the effects of CFTR gene malfunctions. More recently, animal models, such as CRISPR generated sheep and rabbits used in the two current …

Cannabis As A Prescription Opioid Substitute For Adults With Chronic Pain: A Systematic Literature Review, Lani Kranz

All Graduate Theses, Dissertations, and Other Capstone Projects

Objective: To determine whether the use of cannabis improves pain control and/or reduces the amounts of opioids needed to control pain in adults with chronic pain.

Methods: A systematic literature review of research conducted from the past five years. Five databases were searched, resulting in 14 peer-reviewed articles relevant to the objective.

Results: The majority of the literature reviewed demonstrated the use of cannabis by adults with chronic pain resulted in better pain control and/or fewer opioids required to control pain in this population. The two articles which contradicted these findings only evaluated illicit, not medical, cannabis use by individuals …

Effects Of E-Cigarette Vapor On Zebrafish Cell Regeneration And Wound Healing, Alyssa A. Grismer, Jenna E. Pumneo, Brian Bagatto

Williams Honors College, Honors Research Projects

In regards to wound healing, smoking traditional tobacco cigarettes is known to have negative effects on wound healing (Akoz, 2002). An increased risk of skin necrosis has been observed in patients who smoke throughout the surgical process (Akoz, 2002). It is known that nicotine, whether introduced through inhalation or intravenously, leads to peripheral skin vasoconstriction (Akoz, 2002). The full physiological effects of e-cigarettes are not known and research is being done to improve our understanding on the effects that these products may have on our bodies. This research is intended for that purpose. Zebrafish have recently been used as a …

Antibiotic Stewardship In Skin And Soft Tissue Infections, Shah Z. Ali, Jose Campo Maldonado

MEDI 9331 Scholarly Activities Clinical Years

Antibiotic use during inpatient hospitalizations have a significant impact on both patient care and healthcare costs. Using data collected over a one month period in 2019 from inpatient hospitalizations, we aim to determine the most common indicated uses for vancomycin and piperacillin-tazobactam, along with the average days of therapy for their use in treating skin and soft tissue infections.

An Investigation On The Effect Of The Chain Length Of Glutamic Acid Oligomers On The Nucleation, Precipitate Growth, And Phase Transformation Of Amorphous Calcium Phosphate To Crystalline Hydroxyapatite, Emma Harmon

Williams Honors College, Honors Research Projects

This project aims to analyze the effect that the chain length of oligo0glutamic acid sequences has on the nucleation, growth, and phase transformation of amorphous calcium phosphate to crystalline hydroxyapatite. As cited in the formal proposal, hydroxyapatite is the main mineral in bone and dentin and it is of particular interest as a biomaterial. Mineralization is required for much of its structural and protective functioning, however the timing of mineralization is also important for proper growth and development. The presence of glutamic acid containing protein residues impacts the mineralization patterns of hydroxyapatite and this study aims to determine exactly what …

Improving Purification Method Of The F-Plasmid Exclusion Protein Trat, Jazmyn Whitfield, Katelyn Lott, Victor Dunagan

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Reversible Glucan Phosphorylation In The Red Alga, Cyanidioschyzon Merolae, Corey Owen Brizzee

Theses and Dissertations--Molecular and Cellular Biochemistry

Starch and glycogen are an essential component for the majority of species and have been developed to maintain homeostasis in response to environmental changes. Water-soluble glycogen is an excellent source of quick, short-term energy in response to energy demands. In contrast, plants and algae have developed the macromolecule starch that is elegantly suitable for their dependence on external circumstances. Semi-crystalline starch is water-insoluble and inaccessible to most amylolytic enzymes, thus plants and algae have developed a coordinated system so that these enzymes can gain access to the denser starch energy cache. Starch-like semi-crystalline polysaccharides are also found in red algae, …

Cloning And Functional Characterizations Of Circular Rnas From The Human Mapt Locus, Justin R. Welden

Theses and Dissertations--Molecular and Cellular Biochemistry

Under pathophysiological conditions, the microtubule protein tau (MAPT) forms neurofibrillary tangles that are the hallmark of sporadic Alzheimer’s disease as well as familial frontotemporal dementias linked to chromosome 17 (FTDP-17). In this work, I report that MAPT forms circular RNAs through backsplicing of exon 12 to either exon 10 or exon 7 (12→10; 12→7), and that these circular RNAs are translated into proteins.

Using stable cell lines overexpressing the circular tau RNAs 12→7 and 12→10, we have discovered that the tau circular RNA 12→7 is translated in a rolling circle, giving rise to multiple proteins. This circular RNA …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

A Determination Of The Aerosolization Efficiency Of Drugs Of Abuse In A Eutectic Mixture With Nicotine In Electronic Cigarettes, Laerissa Reveil

Master of Science in Forensic Science Directed Research Projects

Electronic cigarettes (e-cigarettes) were originally advertised as an alternative nicotine delivery system to facilitate smoking cessation. However, their popularity for recreational use has increased due to focuses on their trendiness, convenience, and discreteness along with concerns for its use to consume drugs other than nicotine (DOTN). With the adulteration of e-liquids, usually containing nicotine, with other substances, a greater understanding on how DOTN interact with the e-liquid constituents and how they are delivered to the user is necessary. E-liquids were prepared with 50:50 propylene glycol:vegetable glycerin, pure nicotine, pure methadone hydrochloride, and 1:1 methadone hydrochloride:nicotine and aerosolized via an automated …

The Therapeutic Potential Of Glycosaminoglycan Directed Metalloglycomics: Elucidating New Targets And Mechanisms For Polynuclear Platinum Complexes, James D. Hampton

Theses and Dissertations

Cancer remains a serious clinical problem and in order to continue to improve patient health outcomes, novel treatment strategies must continue to be developed. Platinum chemotherapies remain as one of the most widely successful classes of cancer therapeutic, with over 50% of cancer patients receiving a platinate at some point over the span of their treatment. However, intrinsic and extrinsic resistances limit their effectiveness, long term efficacy, and broad applicability to multiple cancer subtypes. Therefore, the development of new agents and strategies which can overcome these limitations are crucial for patient health. To this end a novel class of polynuclear …

Single-Molecule Investigation Of I-Motif Folding And Dynamics In Bioinspired Dna Platforms, Anoja Megalathan

Theses and Dissertations

Although the canonical right-handed B-DNA is the predominant form of DNA in cells, DNA can adopt other secondary structures such as hairpins, G-quadruplexes (G4), and intercalated motifs (i-motif). These secondary structures are typically formed in the regions with repeat sequences. Among many secondary structures DNA can adopt, G-quadruplexes and i-motifs (tetraplex structures formed in the G-rich and C-rich sequences, respectively) caught significant research interest in recent years due to the prevalence of G-rich and C-rich sequences in the human genome. While G-quadruplexes are extensively studied, little is known about i-motifs – especially their formation and stability under cellular environments. For …

Conformational Modulation Of Α-Helical N-Acetylated Α-Synuclein, Ricardo Fernandez

Theses and Dissertations

Human N-acetylated α-synuclein (^NAcαSyn) has long been accepted as an intrinsically disordered protein (IDP) predominantly found in terminal nerve regions in healthy subjects. ^NAcαSyn structural fluidity enables the formation of transient or dynamic assemblies. Some of these assemblies may serve functional, yet undefined purposes. ^NAcαSyn is highly susceptible to the surrounding environment, leading to misfolding under high cytosolic oxidative stress conditions, which in turn assemble in the form of toxic oligomers or amyloid fibrils. These ^NAcαSyn inclusions along with their accretion and migration within neurons, are pathological hallmarks of Parkinson’s disease (PD), dementia, and multiple …