Pharmacy and Pharmaceutical Sciences Commons^™

Development Of Nanoliposomes For The Treatment Of Braf V600e Mutated Parent And Vemurafenib-Resistant Melanoma, Yige Fu

Theses and Dissertations

Melanoma is one of the most aggressive and deadliest types of skin cancer. Currently, off-target toxicities and the rapid resistance development of metastatic melanoma mainly restrict the efficiency of the treatments. This thesis presents efforts towards developing liposomes to address current problems of BRAF-mutant metastatic melanoma.

EphA2-Receptor Targeted PEGylated Nanoliposomes for the Treatment of BRAF V600E Mutated Parent and Resistant Melanoma

In order to address off-target toxicities of the targeted therapy of MEK inhibitor trametinib (TMB), we developed a physically stable EphrinA1-mimicking peptide (YSA) anchored TMB-loaded PEGylated nanoliposomes (YTPLs). The YTPLs were evaluated in BRAFV600E-mutated parent cell lines (A375 and …

Preformulation Studies For The Preparation Of Amorphous Solid Dispersions, Hemanth Kumar Mamidi

Theses and Dissertations

The major challenges in the formulation of amorphous solid dispersions (ASDs) using hot-melt extrusion (HME) are the selection of an ideal polymeric carrier, optimization of HME processing conditions, and screening of the physical stability of the ASDs. Addressing these challenges using traditional approaches require extensive experimentation and large amounts of active pharmaceutical ingredients (API) which may not be feasible during the initial stages of product development. Therefore, there is a need to develop material-sparing techniques for the successful formulation of ASDs. The objective of the present study was to develop material-sparing techniques that can be used as pre-formulation tool during …

Exploring Efficacy Of An Anti-Malarial Nanomedicine In Non-Small Cell Lung Cancer Treatment, Vineela Parvathaneni

Theses and Dissertations

New drug and dosage form development faces significant challenges, especially in oncology, due to longer development cycle and associated scale-up complexities. Repurposing of existing drugs with potential anti-cancer activity into new therapeutic regimens provides a feasible alternative. In this project, amodiaquine (AQ), an anti-malarial drug, has been explored for its anti-cancer efficacy through formulating inhalable nanoparticulate systems using high-pressure homogenization (HPH) with scale-up feasibility and high reproducibility. A 32 multifactorial design was employed to better understand critical processes and formulation parameters so as to ensure product quality with improved anticancer efficacy in non-small cell lung cancer (NSCLC). Optimized AQ loaded …

Development And Characterization Of Bilayer Abuse Deterrent Extended Release Tablet Using Various Model Drugs For Opioids Overdose Crisis, Ankit Soni

Theses and Dissertations

The objective of present study is to develop bilayer abuse-deterrent extended-release tablets (ADERTs) using various model drugs for opioids overdose crisis. Bilayer ADERTs using various model drugs were fabricated by direct compression; consists of extended-release drug layer and pH modifying layer. To develop extended-release layer, various hydrophilic polymers evaluated for their abuse deterrent potential. Based on significantly higher viscosity at 100RPM and lower syringe-ability data, it was found that HPMC K100M could be used as abuse deterrent polymer. Along HPMC K100M, various diluents were evaluated for their abuse deterrent potential. Tablet formulations prepared with various type of diluents using metformin …

Qbd Approach For Development Of Ivermectin-Loaded Gastro Retentive Sustained Release Tablets As Mass Drug Administration For Malaria Transmission Control, Zhangjie Xi

Theses and Dissertations

Malaria is a life-threatening disease with a high prevalence worldwide. Mass drug administration (MDA) of ivermectin have been shown to prevent the transmission of malaria. The objective of this investigation is to develop ivermectin-loaded gastro retentive sustained release tablets (GRSRTs), which have the potential to avoid not only frequent administration of MDA but also fluctuation of ivermectin in systemic circulation. Based on the outcomes from screening various materials to be the suitable matrix forming polymer and bio-adhesive polymer mixture of GRSRTs, HPMC K100M, Carbopol 934p and sodium alginate:chitosan (1:1) were selected as formulation variables. Eight formulations of ivermectin-loaded GRSRTs were …

Double-Coated Biodegradable Poly (Butyl Cyanoacrylate) Nanoparticulate Delivery Systems For Brain Targeting Of Doxorubicin Via Oral Administration, Neeraj Kaushal

Theses and Dissertations

Primary brain cancer cells grow within the brain or cancer cells can metastasis from different site of the body into brain. The major hurdle in the treatment of brain cancer is the presence of blood-brain barrier (BBB). Additionally, acquired multidrug-resistant (MDR) impedes the success of long-term chemotherapy. Therefore, the objective of this investigation is to evaluate the brain targeting potential of orally administered poly(butyl cyanoacrylate) nanoparticulate delivery systems (PBCA-NPDS), double-coated with Tween 80 and polyethylene glycol (PEG) 20000 for brain delivery of doxorubicin, that does not cross the BBB by itself. And, evaluate the MDR reversal potential of PBCA-NPDS. Doxorubicin-loaded …

Up-Regulation Of Fibroblast Growth Factor (Fgf) 21 Via Ap-1 Activation Attenuates Cisplatin-Induced Hepatotoxicity, Yue Zhang

Theses and Dissertations

Fibroblast growth factor (Fgf in rodents and FGF in human) 21 plays important roles in the maintenance of sugar, lipid and energy homeostasis. Fgf/FGF21 can be up-regulated via activation of peroxisome proliferator-activated receptors (PPARs), aryl hydrocarbon receptor (AhR), glucocorticoid receptor (GR), and activating transcription factor (ATF) 4. Recent studies also demonstrated that Fgf/FGF21 plays cytoprotective roles against chemical-induced toxicities, such as of dioxins, acetaminophen, and alcohols. Cisplatin (cis-diamminedichloroplatinum, CDDP) is a widely used chemotherapeutic drug. However, numerous adverse effects have been noted during CDDP therapy, which largely limit its clinical applications. This study was designed to determine the regulation of …

Hot-Melt Extruded Amorphous Solid Dispersion For Solubility, Stability, And Bioavailability Enhancement Of Telmisartan, Bhupendra Raj Giri, Jaewook Kwon, Anh Q. Vo, Ajinkya M. Bhagurkar

Faculty and Student Publications

Telmisartan (TEL, an antihypertensive drug) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its poor aqueous solubility. In this study, we enhanced the solubility, bioavailability, and stability of TEL through the fabrication of TEL-loaded pH-modulated solid dispersion (TEL pHM-SD) using hot-melt extrusion (HME) technology. We prepared different TEL pHM-SD formulations by varying the ratio of the drug (TEL, 10–60% w/w), the hydrophilic polymer (Soluplus®, 30–90% w/w), and pH-modifier (sodium carbonate, 0–10% w/w). More so, the tablets prepared from an optimized formulation (F8) showed a strikingly improved in vitro dissolution profile (~30-fold) compared to the free drug …

Evaluation Of Sacubitril/Valsartan Prescribing Patterns Within An Inpatient Hospital Setting, Megan Taylor Pharmd, Katie Nesbitt Pharmd, Bcps

Department of Pharmacy

No abstract provided.

Evaluation Of Student Pharmacists’ Attitudes And Perceptions Of Hormonal Contraception Prescribing In Indiana, J. Henry Papineau, Jenny L. Newlon, Ryan S. Ades, Veronica Vernon, Tracey A. Wilkinson, Lynn M. Thoma, Ashley H. Meredith

Scholarship and Professional Work – COPHS

Community pharmacists’ scope of practice is expanding to include hormonal contraceptive prescribing. Prior to introducing statewide legislation, it is important to assess the perceptions of future pharmacists. A cross-sectional survey was distributed to 651 third- and fourth-year professional students enrolled at three colleges of pharmacy in Indiana. Data were collected between September and October 2019 to assess students’ attitudes about prescribing hormonal contraceptives, readiness to prescribe, perceived barriers, and desire for additional training. In total, 20.9% (n = 136) students responded. Most (89%, n = 121) believe that pharmacist-prescribed hormonal contraceptives would be beneficial to women in Indiana, and 91% …

Pharmacists’ Perceptions And Attitudes Toward Drug Importation Into The State Of Florida, John Hertig, Jade M. Jochem, Allissa M. Long

Scholarship and Professional Work – COPHS

Background: The Department of Health and Human Services and the Food and Drug Administration released the Safe Importation Action Plan in July 2020 detailing methods to import medicines from Canada to combat increasing drug costs. In November 2020, Florida became the first state in the United States to create and propose an importation plan from Canada. This study examines the proposal submitted by Florida, Florida pharmacists’ perceptions of the program on patient safety, and Florida pharmacists’ thoughts on the pharmacy operational impact.

Methods: This was a cross-sectional study utilizing an electronic questionnaire sent to pharmacist members of the Florida Pharmacy …

The Relationship Between Fake News And Fake Medicines: How Misinformation Has Fuelled The Sale Of Covid-19 Substandard And Falsified Medical Products, Oksana Pyzik, John Hertig, Hoda Kanso, Anika Chamba, Sofia Khan

Scholarship and Professional Work – COPHS

As waves of COVID-19 continue to threaten public health, an increasing volume of disease related information is widely accessible, and not all of it is accurate or reliable. The World Health Organisation (WHO) described this overabundance of information, misinformation, and disinformation as an "infodemic", making it difficult for many to distinguish fact from fiction. These definitions are complex and transitional; however, misinformation is defined as the "inadvertent sharing of false information", whereas disinformation is more sinister in origin and constitutes "the deliberate creation and sharing of information known to be false." The infodemic encapsulates both intentional and unintentional erroneous sources. …

Alterations In Gene Expression Of Renin-Angiotensin System Components And Related Proteins In Colorectal Cancer, Danial Mehranfard, Gabriela Perez, Andres Rodriguez, Julia M. Ladna, Christopher T. Neagra, Benjamin Goldstein, Timothy Carroll, Alice Tran, Malav Trivedi, Robert C. Speth

HPD Articles

MATERIALS AND METHODS: Quantitative expression of the RNA of these 17 genes in normal and cancerous tissues obtained using chip arrays from the public functional genomics data repository, Gene Expression Omnibus (GEO) application, was compared statistically. RESULTS: Expression of four genes, (angiotensinogen), (aminopeptidase A) (neprilysin), and (prolyl endopeptidase), was significantly upregulated in CRC specimens. Expression of (renin), (thimet oligopeptidase), (neurolysin), (prolyl carboxypeptidase), (aminopeptidase N), and (Mas receptor) was downregulated in CRC specimens. CONCLUSIONS: Presuming gene expression parallel protein expression, these results suggest that increased production of the angiotensinogen precursor of angiotensin (ANG) peptides, with the reduction of the enzymes that …

The Impact Of Perfectionism On Well-Being: Shame In Perfectionism’S Influence On Emotion Regulation, Vishal Ravindra Rathod

Selected Full-Text Dissertations 2020-

Combined product development strategy of antisolvent precipitation and spray drying was adopted to create a hybridized redispersible spray dried ritonavir (RTV, BCS Class IV) nanoamorphous micellar dispersion (RTV-rSD-NAMD) to enhance the solubility and masked the bitterness of RTV. Initially, a proof of concept study was designed using DM3 research strategy to develop RTV-NAMD. It was employed in conjunction with the quality-by-design spaces, and quality target product profile to link the critical material attributes and critical process parameters to the quality target product profile’s critical product attributes QbD elements. RTV-NAMD was successfully optimized with Soluplus® as the stabilizer using the response …

Ketamine Infusions For Post-Cesarean Pain In Patients With Opioid Use Disorder, Talitha Budi, Johanna Cobb, Wendy Craig, Heather Turcotte, Janelle Richard, Aurora Quaye

Costas T. Lambrew Research Retreat 2021

Discussion:

• Opioid consumption may be reduced during ketamine infusion without significant side effects

• Further investigation planned with a prospective, randomized, double-blind, placebo-controlled trial.

Safe Injection To Prevent Infection: Specific Injection Practices Are Associated With Hepatitis C Exposure, Suggesting Opportunities For Targeted Harm Reduction Intervention For People Who Inject Drugs In Maine, N P. Sankar, K Murray, D Burris, K Thakarar

Costas T. Lambrew Research Retreat 2021

Background

• The U.S. opioid epidemic has contributed to an increase in infections related to IDU, such as HCV

• Transmission of HCV has been linked to unsafe injection practices

• This study aims to characterize risk factors associated with HCV exposure amongst people who inject drugs in Maine Methods

Preventive Healthcare Services Receipt And Primary Care Provider Utilization Among People Who Inject Drugs, E K. Nenninger, Kinna Thakarar

Costas T. Lambrew Research Retreat 2021

Introduction:

People who inject drugs (PWID) face barriers to accessing primary care providers (PCPs) and preventive services, but are at increased risk for preventable infections

Preventive services can be accessed through PCPs, or while hospitalized or at community organizations like syringe service programs (SSPs)

The Development Of A Cancer-Targeting Peptide-Drug Conjugate For The Treatment Of Melanoma, Cassandra Dill

Pharmaceutical Sciences (MS) Theses

Cancer is an ongoing global pandemic which has caused a dramatic shift in research priorities. One of the most aggressive and difficult to treat has invariably remained metastatic melanoma. Although encompassing only 4% of overall skin cancer diagnoses, chances for recovery were slim until recent revolutionary development of immunotherapy adding to its regimen spectrum. This is due to its resistance to many standard-of-care treatment methods, along with its relatively high-metastatic potential. Within the past decade, eight new targeted and immune checkpoint inhibitors have gained FDA approval. The median life survival has increased significantly from 9 months to over 2 years …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

Meta-Analysis Comparing Direct Oral Anticoagulants Versus Vitamin K Antagonists In Patients With Left Ventricular Thrombus, Kazuhiko Kido, Yasir Abdul Ghaffar, James C. Lee, Christopher Bianco, Mikiko Shimizu, Tsuyoshi Shiga, Masayuki Hashiguchi

Faculty & Staff Scholarship

Current American College of Cardiology/American Heart Association guidelines for stroke or ST-elevation myocardial infarction recommend the use of oral vitamin K antagonists (VKAs) as a first-line anticoagulant. Although several studies have compared the use of direct oral anticoagulants (DOACs) to VKAs for left ventricular thrombus (LVT) anticoagula- tion therapy, they are small scale and have produced conflicting results. Thus, this meta- analysis was performed to aggregate these studies to better compare the efficacy and safety of DOACs with VKAs in patients with LVT. Cochrane Library, Google Scholar, MED- LINE, and Web of Science database searches through January 10, 2021 were …

Viral Factors Influencing Early Infection Events During Ex-Vivo Kshv Infection, Ramina Nabiee

Pharmaceutical Sciences (PhD) Dissertations

The enigma of Kaposi Sarcoma Herpes Virus infection, and its persistence despite a quarter century of research on the virus, has given rise to an immediate need for addressing fundamental questions about basic immunology and virology knowledge regarding this virus. Kaposi Sarcoma Herpes Virus (KSHV), also known as Human Herpesvirus 8 (HHV8), is the etiological agent of Kaposi Sarcoma (KS) and other lymphoproliferative cancers, such as Multicentric Castleman’s Disease (MCD), Primary Effusion Lymphoma (PEL), and a newly discovered rare disease called KSHV Inflammatory Cytokines Syndrome (KICS). Epidemic KS, also known as AIDS-KS, is the most common cancer in untreated HIV …

Aldo-Keto Reductases And Cancer Drug Resistance, Trevor M. Penning, Sravan Jonnalagadda, Paul C. Trippier, Tea Lanišnik Rižner

Journal Articles: Pharmaceutical Sciences

Human aldo-keto reductases (AKRs) catalyze the NADPH-dependent reduction of carbonyl groups to alcohols for conjugation reactions to proceed. They are implicated in resistance to cancer chemotherapeutic agents either because they are directly involved in their metabolism or help eradicate the cellular stress created by these agents (e.g., reactive oxygen species and lipid peroxides). Furthermore, this cellular stress activates the Nuclear factor-erythroid 2 p45-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 pathway. As many human AKR genes are upregulated by the NRF2 transcription factor, this leads to a feed-forward mechanism to enhance drug resistance. Resistance to major classes of chemotherapeutic agents (anthracyclines, …

Site-Search Process For Synaptic Protein-Dna Complexes, Sridhar Vemulapalli, Mohtadin Hashemi, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

The assembly of synaptic protein-DNA complexes by specialized proteins is critical for bringing together two distant sites within a DNA molecule or bridging two DNA molecules. The assembly of such synaptosomes is needed in numerous genetic processes requiring the interactions of two or more sites. The molecular mechanisms by which the protein brings the sites together, enabling the assembly of synaptosomes, remain unknown. Such proteins can utilize sliding, jumping, and segmental transfer pathways proposed for the single-site search process, but none of these pathways explains how the synaptosome assembles. Here we used restriction enzyme SfiI, that requires the assembly of …

Sex-Specific Gene Expression In Flupirtine-Treated Cln3Δex7/8 Mouse Brain, Joelle Makoukji, Sara Saab, Katia Maalouf, Nadine J. Makhoul, Angelica V. Carmona, Nihar Kinarivala, Paul C. Trippier, Rose-Mary Boustany

Journal Articles: Pharmaceutical Sciences

Gene expression is a powerful tool to understand structure-function relationships in the nervous system. This study reports global gene expression changes induced by flupirtine in brain of male and female Cln3Δex7/8 mice, exposing potential flupirtine targets at the molecular level. Gene expression analysis of male and female Cln3Δex7/8 mouse brain was determined following oral administration of flupirtine for 14 weeks, using Mouse Genome 430 2.0 array Chips and an Affymetrix platform. Fifty-six genes in males and 79 in females were differentially expressed in flupirtine- versus vehicle-treated Cln3Δex7/8 mouse brain. Flupirtine altered several pathways in Cln3Δex7/8 mouse brain: apoptosis, the complement …

Medication Use Evaluation Of Ceftriaxone Dosing In Pediatric Patients, Sara Frey Pharmd, Kristin M. Held Wheatley Pharmd, Bcop

Department of Pharmacy

No abstract provided.

Comparison Of The Therapeutic Efficacy Of Rheumatoid Arthritis Treatments, Kacy Smith Davis

Walden Dissertations and Doctoral Studies

Rheumatoid arthritis (RA) is an autoimmune condition that causes chronic joint pain and destruction. The current standard regimen of monotherapy disease modifying anti-rheumatic drug (DMARD) treatments may not be as effective as that of combination therapy of a DMARD and a biologic agent in treating RA. The purpose of this study was to answer the question, is there a difference in the therapeutic efficacy of combination DMARD treatments with a biologic, compared to monotherapy DMARDs without a biologic, in U.S. Caucasian women between the ages of 30 and 60 that have been diagnosed with RA? Guided by the theoretical framework …

A Semiparametric Modeling Approach For Analyzing Clinical Biomarkers Restricted To Limits Of Detection, Sandipan Dutta, Susan Halabi

Mathematics & Statistics Faculty Publications

Before biomarkers can be used in clinical trials or patients' management, the laboratory assays that measure their levels have to go through development and analytical validation. One of the most critical performance metrics for validation of any assay is related to the minimum amount of values that can be detected and any value below this limit is referred to as below the limit of detection (LOD). Most of the existing approaches that model such biomarkers, restricted by LOD, are parametric in nature. These parametric models, however, heavily depend on the distributional assumptions, and can result in loss of precision under …

Development Of An Online Warfarin Dosing Platform Using R Programming Language To Facilitate Healthcare Professional Duties And Limit Medication Related Errors., Monther Alsultan

Graduate Research Posters

Development of an online warfarin dosing platform using R programming language to facilitate healthcare professional duties and limit medication related errors.

Monther Alsultan, Joshua M. Morriss, Daniel Contaifer Jr, Suad Alshammari; Silas Contaifer, Rachel W Flurie, Dayanjan S. Wijesinghe^#

Department of Pharmacotherapy and Outcome Sciences

Objective: 1) Gain experience in developing platform agnostic, fully operational and clinically relevant web applications for effective pharmacist led patient care. 2) Create a decision- support tool using open source software to facilitate evidence-based management therapy of warfarin in clinical settings where it is available for everyone to use at anytime and anywhere.

Introduction: …

Frequency Of Genetic Polymorphisms Of Cyp2c19 In Native Hawaiian, And Asian And Pacific Islander Subgroups: Implications For Personalized Medicine, Khalifa Y. Alrajeh, Youssef Roman Dr

Graduate Research Posters

Pharmacogenetic testing, where prescriptions are tailored to the individual patient based on his/her genetic makeup, increases the ability to predict individual drug response. However, little is known about the prevalence of clinically actionable pharmacogenes in diverse populations. This study seeks to assess the prevalence of select drug-gene alleles that are implicated in the metabolism of commonly prescribed drugs, so-called Very Important Pharmacogenes (VIPs). The results of this study will fill in the gaps of knowledge of VIPs in underrepresented populations and characterize their potential risk for drug adverse events or due to their underlying genetic polymorphisms, especially in patients of …

Pharmacogenomics And Ssris Appropriateness In Older Community Dwelling African Americans, Wint War Phyo, Lana Sargent, Elvin T. Price

Graduate Research Posters

Background: Depressive and anxiety disorders are among the most common illnesses experienced by older adults (age > 60). The selective serotonin reuptake inhibitors (SSRIs) are preferred class of antidepressants for these disorders due to their high efficacy and safety profiles among older adults. However, SSRIs are metabolized by highly polymorphic cytochrome P450 enzymes, specifically CYP2D6 and CYP2C19. This can lead to variable dose-response outcomes, especially among older African American population.

Objective: Analyze the frequency of CYP2D6 and CYP2C19 polymorphisms in African American older adults who are taking SSRIs and identify potential inappropriate use of SSRIs in these older adults using the …