Pharmacy and Pharmaceutical Sciences Commons^™

Development, Optimization, And In Vitro Characterization Of Different Anesthetic Wound Products, Alia Alshammari

Electronic Theses and Dissertations

ABSTRACTAcute and chronic wounds can be a significant source of pain. In the past, pain associated with chronic wounds has been perceived as an inevitable complication of wound care. Fortunately, recent approaches in wound care have developed strategies to prevent and reduce pain when carrying out wound care. Local anesthetics have been used to that end. Lidocaine is the most widely used topical anesthetic in wound care. However, literature on topical Lidocaine has focused almost exclusively on the clinical application on intact skin. This dissertation aims to advance our understanding of anesthetic wound product formulation and development. Anesthetic wound ointments …

Sleep And Health-Related Quality Of Life Among Persons With Parkinson’S Disease And Their Caregiverssleep And Health-Related Quality Of Life Among Persons With Parkinson’S Disease And Their Caregivers, Sushmitha Inguva

Electronic Theses and Dissertations

This dissertation aimed at filling gaps in the body of Parkinson’s disease (PD) and sleep literature by synthesizing and appraising current knowledge on the influence of sleep on health-related quality of life (HRQoL) in persons with Parkinson’s (PWP) and their caregivers, conducting a psychometric evaluation of a HRQoL instrument among PWP, and applying a novel method to assess the dyadic relationship between sleep and HRQoL in PWP and their caregivers. First, the systematic literature review results showed that nocturnal and diurnal sleep problems among PWP are strong predictors of their HRQoL. Additionally, studies that focused on caregiver outcomes showed that …

Computational Modeling Of Non-Active Functional States Of The Cannabinoid Receptor 1 And Its Ligands, Ayooluwa Olufunmi Aderibigbe

Electronic Theses and Dissertations

The cannabinoid receptor 1 (CB1) is a class A G-protein coupled receptor that is implicated in a variety of physiological processes, such as energy homeostasis, appetite regulation, cognition and motor control, and mood regulation. CB1 is widely distributed throughout the body, but is mainly expressed in the brain. Molecules that reduce CB1 signaling exhibit anti-obesity properties due to their effect in reducing appetite and body weight gain. However, the consequence of reducing CB1 signaling in the CNS includes adverse neuropsychiatric effects such as depression and suicidal ideation. Two methods of scientific interest for developing CB1 antagonists as anti-obesity drugs are …

Development Of Site - Specific Drug Delivery Systems Using Hot Melt Extrusion And Fused Deposition Modeling 3d Printing, Nagireddy Reddy Dumpa

Electronic Theses and Dissertations

Due to preferential site of drug absorption and the need for increased concentration of medication at the required tissues, dosage forms should be designed or formulated in such a way that medication is released at a specific site or after a specific time in the gastrointestinal tract (GIT). Knowledge of transit times of dosage forms in each part of GIT, by use of particular polymers or employing specific delivery systems such as floating systems, delivery of medication to specific sites in the GIT can be achieved. HME coupled FDM 3D printing has the capability to create customized dosage forms for …

Nmr-Based Characterization Of A Glucan Isolated From Ganoderma Lucidum, Alysia Gonzales

Electronic Theses and Dissertations

Ganoderma lucidum is a polypore fungus commonly known as Lingzhi, Youngji or Reishi mushroom in East Asia. It is frequently marketed as an herbal supplement and often utilized as traditional Chinese medicine. Our research comprises the structural investigation of the principal polysaccharide from this fungus. After proper purification, the fungal glucan was subjected to multiple experiments of NMR spectroscopy, including 1D 1H and 13C, 2D; 1H-1H COSY, 1H-1H TOCSY, 1H-1H NOESY, 1H-13C HSQC, 1H-1H Phase Sensitive-TOCSY, and 1H-13C TOCSY-HSQC NMR spectra. Data has confirmed that this fungal polysaccharide contains residues of glucose (91.31%) as major, galactose (4.99%), and mannose (3.69%) …

Towards A New Method Of Determining Protein Structure, Niloofar Abolhasani Khaje

Electronic Theses and Dissertations

Hydroxyl radical protein footprinting (HRPF) by fast photochemical oxidation of proteins (FPOP) is a mass spectrometry-based technique that measures the apparent protein oxidation rate by freely diffusing hydroxyl radicals at different regions in a protein, and correlates changes in this apparent rate with changes in the solvent accessibility of the protein target based on quantifying the amount of oxidation of different regions of a protein. While there have been many advancements in HRPF-FPOP, oxidation measurement still suffers from high variability between measurements. High variability reduces the power statistical power this technique even in the presence of radical dosimetry measurements and …

Design And Synthesis Of Salvinorin-Based Compounds For The Opioid Receptors., Nicholas S. Akins

Electronic Theses and Dissertations

Opioid receptors (OR) are expressed throughout both the peripheral and central nervous system and play crucial roles in the modulation of antinociception, addiction, anxiety, and depression. Salvinorin A, the main isolate of the hallucinogenic plant Salvia divinorum, is one of the most potent naturally occurring kappa opioid receptor agonists. Salvinorin A possesses beneficial effects as a therapeutic in a variety of CNS disorders, but due to its strong hallucinating, anxiogenic effects, and short half-life(t1/2), it has never advanced to clinical trials. Instead, salvinorin A has been used as an important prototype for the development of related drug candidates. Our initial …

Abuse Deterrent Formulation Using Hot Melt Extrusion Technology, Vishvesh Raje

Electronic Theses and Dissertations

The purpose of the current study was to formulate hot melt extruded (HME) abuse deterrent pellets of acetaminophen(APAP), a model drug with the aid of high molecular weight hydroxypropyl methylcellulose (HPMC 4M ) and gelling agents (starch, pectin and carbopol). The formulated HME pellets were assessed for their abuse-deterrence (AD) potential using Category- 1 laboratory in-vitro evaluation standards. The pellets were examined for the particle size reduction (PSR), extraction in small volume, syringeability, thermal manipulation and dissolution for evaluating the resilience of the AD properties. Though, most of the formulation showed complete particle size reduction after grinding, grounded pellets were …

Applications Of Hot-Melt Extrusion (Hme) Technology And Investigation Of A Screening Tool For Hme, Gauri Deepak Shadambikar

Electronic Theses and Dissertations

Hot-melt extrusion (HME), an adaptable technology, has established its position in manufacturing operations like amorphous solid dispersions, immediate and controlled oral formulations, implants and taste masked products. In recent years the industrial focus has shifted towards continuous manufacturing, thus HME is being explored for new applications. The aim of this research was to investigate the novel applications of HME by carrying out an in-depth study to understand the interaction between the process and product and to investigate a screening tool for its small-scale formulation and development.As HME consumes large amount of samples during the developmental phase, we investigated a screening …

An In-Depth Approach For Functional Oligosaccharide Analysis, Hao Liu

Electronic Theses and Dissertations

Heparin and heparan sulfate (Hp/HS) are linear complex glycosaminoglycans (GAGs), which are involved in diverse biological processes. Although Hp/HS GAGs influence numerous physiological and pathophysiological processes, their high degree of size polydispersity and sequence microheterogeneity make structure-function characterization challenging. In addition, it is hard to understand the structures that underlie any of the various functions with MS, because of the lability of the sulfate group during tandem mass spectrometry (MS/MS) analysis. The work presented here describes an in-depth approach for functional oligosaccharide characterization including chemical derivatization of Hp to inhibit COVID-19 infection, multi-dimensional liquid chromatography (LC) fractionation method, chemical derivatization …

The Empirical Journey On The Roads Less Traveled To Explore The Concept Of Medication Competence And Address Nursing Students’ Pharmacology Self-Efficacy, Melynda Thelen

Electronic Theses and Dissertations

Medication competence is a priority within the academic setting, as it allows nurses to provide sound knowledge-based care and ensure safe medication delivery. Nevertheless, there is a dearth of theoretical or conceptual basis and definition of medication competence to guide assessment, analysis, and development of informed empirical evidence. Literature has also suggested current curricula do not support the complex and in-depth nature of nursing pharmacology. This dissertation paper presents three seminal manuscripts which provides the researcher’s pathway in discovering and analyzing an innovative nursing pharmacology educational strategy. The first manuscript focused on a concept analysis on medication competence, which provided …

Design And Synthesis Of Pyrimidine Based Fused Heterocyclics In The Potential Treatment Of Cancer And Opportunistic Infection, Farhana Islam

Electronic Theses and Dissertations

Dose-limiting toxicities of clinically used agents and development of resistance are two significant limitations in cancer chemotherapy. Microtubule targeting agents (MTAs) are a structurally diverse set of compounds that disrupt microtubule dynamics and exert their anticancer effect. Combination chemotherapy with antiangiogenic agents and microtubule targeting agents has shown an advantage against both these drawbacks. Single agents with dual antiangiogenic activity and cytotoxicity would afford a therapy that circumvents pharmacokinetic problems of multiple agents, avoid drug-drug interactions, lower the drug dose, decrease overlapping toxicities, and delay or prevent tumor cell resistance. The work in this dissertation reflects the progress of fused …

Pharmacological Characterization Of Novel Serotonin Transporter Inhibitors Identified Through Computational Structure-Based Virtual Screening, Michael Wasko

Electronic Theses and Dissertations

Depression is a mental health disorder affecting greater than 350 million people worldwide with roughly 7% of the United States population diagnosed as of 2017. The selective serotonin reuptake inhibitors (SSRIs) have been the mainstay of pharmacotherapies for depression for the last 40 years. The SSRIs target the serotonin transporter (SERT), a monoamine transporter (MAT) responsible for terminating serotonergic neurotransmission. The SSRIs are not perfect therapeutics and suffer from delayed response times, inconsistent efficacy among patients, and often produce intolerable side effects. Therefore, a strong need exists to develop new antidepressants that are more efficacious and have fewer adverse effects. …

Retrospective Cohort Study Of Patients With Chronic Low Back Pain In An Outpatient Pain Specialist Clinic, Gauri Desai

Electronic Theses and Dissertations

Background: Chronic low back pain (LBP) is a back pain that lasts for three or more than three months in the lumbar region of the spinal cord. A nerve injury or damage in the spinal cord region (neuropathic pain) requires multimodal treatment approach for pain reduction. With various treatment options utilized in the pain management of these patients, identifying demographical and clinical characteristics of patients with chronic LBP utilizing interventional procedures and pharmacologic treatments is imperative.

Objective: (i) To describe the demographics (age, gender, race, ethnicity, smoking status, alcohol consumption status, drug use status) and clinical characteristics (procedures, medications) …

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapies In Cystic Fibrosis: A Retrospective Evaluation Of A Nationwide Specialty Pharmacy Database, Zumi Mehta

Electronic Theses and Dissertations

Background: Cystic fibrosis (CF) is a progressive, genetic disorder caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Patients with CF experience excessive mucus build up and infections leading to complications in the pancreas, lungs, and other organs. There has been a paradigm shift in the treatment of CF with the introduction of CFTR modulator therapies and given their high acquisition cost, assessing their economic burden along with the adherence rate of patients is imperative. Objective: (i) To assess the utilization of CFTR modulator therapies in a specialty pharmacy CF patient population and (ii) to calculate …

Gene Delivery To The Blood-Brain Barrier For Ischemic Stroke Therapy, Wanzhu Zhao

Electronic Theses and Dissertations

Stroke is a major cause of death in the United States. We aim to develop safe and efficient approaches for the treatment of stroke. Regenerative therapies have been identified as the major need for curing stroke [1]. We explored two different carriers (poly (ethylene glycol)_5k-poly (L-aspartate-diethylenetriamine)₄₈ (PEG-DET) / Pluronic P84 (P84) and exosomes (EXOs) / microvesicles (MVs)) to deliver brain-derived neurotrophic factor (BDNF) plasmid DNA (pDNA), a functional gene encoding a neurotrophin. In the first project, our data showed that DNA nanoparticles (NPs) with 0.03% P84 was a promising formulation to deliver Luciferase pDNA into immortalized human …

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …

Sulforaphane Protects Against Ethanol-Induced Apoptosis And Teratogenesis Through Epigenetic Modulation Of Anti-Apoptotic Genes., Yihong Li

Electronic Theses and Dissertations

Background. Ethanol-induced excessive apoptosis in neural crest cells (NCCs), a multipotent progenitor cell population, is one of the major mechanisms underlying the pathogenesis of Fetal Alcohol Spectrum Disorders (FASD). However, the molecular mechanisms underlying FASD that results from maternal alcohol exposure during pregnancy are poorly understood. The overall goals of this study are to examine the mechanisms by which ethanol induces apoptosis and malformations in vitro and in vivo, and to develop a nutritional-based approach by using SFN and SFN-rich BSE to prevent FASD through epigenetic modulation. Results. This study demonstrates that ethanol exposure resulted in a significant increase …

Profiling Transcription And Retrotransposition Of Mouse L1 Subfamilies, Lingqi Kong

Electronic Theses and Dissertations

Transposable elements, also called jumping genes, comprise almost 45% of the human genome. In contrast, only 1% of the human genome is protein-coding sequences. The function and advantages of maintaining such massive copies of transposable elements in the human genome are still unclear. Long interspersed element 1 (L1), the most substantial group and the only active autonomous transposable element in the human genome, has revealed its unique roles in many diseases. The insertional mutagenesis induced by L1 retrotransposition events could threaten human genomic stability and generate unexpected mutations. L1 overexpression has been documented in both somatic and germline cells and, …

Design, Synthesis, & Biological Evaluation Of Novel Het-Aromatic/Aromatic Analogs For The Treatment Of Hiv, Cancer, & Cognitive Dysfunctions, Mohit Gupta

Electronic Theses and Dissertations

Cyclophilin A are a class of peptidyl-prolyl isomerases that catalyzes isomerization of the proline residue within a protein. Cyclophilin A plays an instrumental role in the pathogenesis of HIV and HCV virus. Using structure-based drug we designed and synthesized small molecule inhibitors of cyclophilin A. These inhibitors were biologically evaluated for their ability to inhibit WT HIV-1 inhibition.

Mitogen-Activated Protein Kinase signaling cascades plays a critical role in cancer cell survival, metastasis, and chemo-resistance. The MEK5/ERK5 pathway, which is a member of MAPK signaling cascade, is involved in cell survival, anti-apoptotic signaling, angiogenesis, and cell motility. It is found to …

Patient Satisfaction With Substance Use Disorder Rehabilitation Services, Trupti Dhumal

Electronic Theses and Dissertations

Background: Patient satisfaction is considered as an important indicator in the evaluation of healthcare quality across an array of treatments and services. It is deemed vital especially in the field of substance use disorder (SUD) research due to an increased emphasis on understanding patients’ perceptions regarding their treatment and the attributes that drive their progress towards recovery. Despite the potential value, gaps have been recognized in the exploration of these satisfaction-related assessments among patients undergoing SUD treatment in residential rehabilitative settings. Thus, there is a need for understanding the dimensions contributing to satisfaction which would facilitate the development of …

A Recombinant Cholera Toxin B Subunit Variant (Ctb-Kdel) Exhibits Unique Colon Mucosal Healing Effects That Have Therapeutic Implications For Inflammatory Bowel Disease., Joshua Mark Royal

Electronic Theses and Dissertations

This dissertation uncovers the mechanism and explores the utility of a recombinant cholera toxin B subunit (CTB) variant containing a KDEL endoplasmic reticulum (ER) retention motif (CTB-KDEL) as a drug candidate for the treatment of inflammatory bowel disease (IBD). CTB is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine) and vaccine development for decades. On the other hand, several studies have investigated CTB’s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn’s disease and asthma. Here, we reveal …

Structure Elucidation Of A Pyrrolobenzodiazepine Alkaloid And A Biologically Active Polyketide Produced By Rhodococcus Sp. Mtm3w5.2 Via Two-Dimensional Nmr Spectroscopy, Garrett Johnson

Electronic Theses and Dissertations

As the battle against ever-increasing drug resistence bacteria rages on, novel and sometimes more complex natural products can be used to combat this. In this study, two-dimensional NMR techniques were utilized to collect a complete spectral data set for two natural products. The first structure, a synthesized Pyrrolobenzodiazepine alkaloid natural product was confirmed through these methods. The second, a strain of Rhodococcus, MTM3W5.2, produces a novel antibacterial molecule in broth cultures and the active compound was fractionated using a Sephedex LH-20 column. Chromatographic purification yielded a pure sample at 58.90 minutes, RT.58. HRMS data deduced an exact mass of …

Design And Synthesis Of Pyrimidine Based Heterocycles As Potential Anti-Cancer Agents With Combination Chemotherapeutic Potential Or Targeted One Carbon Metabolism Inhibition And Anti-Opportunistic Agents, Arpit Doshi

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic, bicyclic and tricyclic pyrimidine-based heterocycles as a) single agents with combination chemotherapy potential having dual antiangiogenic effects and cytotoxic effects or b) one-carbon metabolism inhibitors for targeted tumor therapy; or c) selective Pneumocystis jirovecii (pj) dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization or thymidylate synthase as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), epidermal growth …

A Quantitative Study Of Drug Recrystallization In Drug-In-Adhesive Transdermal Patches Using Vibrational Spectroscopy, Yi Li

Electronic Theses and Dissertations

Drug-in-adhesive (DIA) transdermal patches are an important type of transdermal drug delivery system (TDDS). The drugs used in the DIA system are frequently present in metastable forms, such as amorphous solids or supercooled liquids. These drug states are thermodynamically unstable and tend to undergo recrystallization. Recrystallization of the active pharmaceutical ingredient can adversely affect the efficacy of transdermal products. This dissertation demonstrates a systematic approach to quantify the crystalline content of the API in DIA systems. This approach uses a novel method of preparing calibration standards and a spectroscopic method to reliably predict crystalline content in DIA patches. Spectroscopic tools, …

Dual Inhibition Of The Pi3k/Akt And Mek5/Erk5 Pathways For The Treatment Of Breast Cancer, Thomas Douglas Wright

Electronic Theses and Dissertations

Breast cancer is a heterogeneous disease state with several challenging frontiers. In particular, aberrations in the Phosphoinositide-3-kinase (PI3K) and Mitogen Activated Protein Kinase (MAPK) pathways have been linked to increased breast cancer proliferation and survival. It has been proposed that these survival characteristics are enhanced through compensatory signaling and crosstalk mechanisms. New evidence suggests that MEK5/ERK5, a member of the MAPK family, is a crucial component in the proliferation and survival of several aggressive cancers. We hypothesize that inhibiting both PI3K/Akt and MEK5/ERK5 pathways will decrease cell viability while maintaining limited collateral toxicity. In this study, we examined the effects …

The Development Of Hybrid Process Control Systems For Fluidized Bed Pellet Coating Processes, Hanzhou Feng

Electronic Theses and Dissertations

The conventional basic control for pharmaceutical batch processes has several drawbacks. The basic control often uses constant process settings discovered by trial and error. The rigid process operation provides limited process understanding and forgoes the opportunities of process optimization. Product quality attributes are measured by the low efficient off-line tests, therefore these cannot be used to monitor and inform the process to make appropriate adjustments. Frequent reprocessing and batch failures are possible consequences if the process is not under effective control. These issues raise serious concerns of the process capability of a pharmaceutical manufacturing process.

An alternative process control strategy …

Modeling And Prediction Of Amorphous Solid Dispersion Formation Using A Molecular Descriptor, Kevin Deboyace

Electronic Theses and Dissertations

Poor aqueous solubility of an active pharmaceutical ingredient (API) is a significant hurdle during drug development. Delivering a drug in its amorphous solid-state is a potential method to overcome this issue, since the amorphous form has increased apparent aqueous solubility. However, the amorphous state is only metastable, and is thermodynamically driven to recrystallize. As a result, pure amorphous drugs are seldom used in marketed products. Intimately mixing a drug in its amorphous form with a polymer, known as an amorphous solid dispersion (ASD), has the potential to significantly extend the physical stability of the amorphous form, while maintaining the benefit …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

Optimization And Characterization Of Hot-Melt Extruded Anti-Inflammatory And Local Anesthetic Bio-Adhesive Semisolid Formulation Using Design Of Experiments (Doe), Rishi Chinmay Thakkar

Electronic Theses and Dissertations

Hot melt extrusion is a versatile continuous manufacturing process extensively investigated for its applications with production of oral solid dosage forms, the aim of this study was to venture the applicability of HME in continuous manufacturing of topical semi-solid ointment formulations. Novel combination of a topical corticosteroid (Triamcinolone Acetonide) and local anesthetic (Lidocaine hydrochloride) were selected to be formulated with a water-soluble ointment base consisting of PEG 4000, PEG 1500 and Propylene glycol after performing appropriate drug-excipient compatibility studies. To determine the ratios of the solid to liquid components of the macrogol base, ‘quality by design’ approach was employed by …