Pharmacy and Pharmaceutical Sciences Commons^™

Charge-Based Optimization Of Neurotensin For Neurotensin-Receptor-1 Targeting Utilizing A One-Bead One-Compound Peptide Library Approach, Trey Neeley

Theses & Dissertations

Neurotensin-receptor-1 (NTSR1) is regularly overexpressed in various cancers and contributes to the proliferation, survival, migration, invasion, and angiogenesis of tumors. NTSR1-targeting vectors have demonstrated promise in both diagnostic and therapeutic aspects. Unfortunately, the relatively poor in vivo metabolic stability and high renal uptake and retention of NTSR1-targeted compounds have hampered the translation to the clinic. In this research, we utilized a one-bead one-compound (OBOC) peptide library approach to make targeted modifications at the naturally charged residues of an NTS (4-13) sequence to discover an NTS derivative with comparable affinity to NTSR1, acceptable in vivo stability, and tolerable renal retention. Subsequent …

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

The Development Of Hyaluronan-Based Contract Agents For The Intraoperative Detection Of Pancreatic Tumors, Bowen Qi

Theses & Dissertations

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. Tumor-specific intraoperative fluorescence imaging could improve staging and surgical resection, thereby improving prognosis. In the first study, hyaluronic acid derived NPs with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG accumulated significantly in an orthotopic pancreatic ductal adenocarcinoma model with safety profile both in vitro and in vivo. To maximize tumor signal, while minimizing signal in healthy pancreas and RES capture of macromolecules, in the next study, we describe the rational …

Engineering Hyaluronic Acid For Biomedical Applications, Deep S. Bhattacharya

Theses & Dissertations

This work presents research using the naturally available non- sulfated carbohydrate glycosaminoglycan hyaluronic acid (HA) for the synthesis of different chemical derivatives of HA for evaluation of binding kinetics with CD44 and P- selectin proteins for applications in fluorescence image-guided surgery. Chemical derivatives of HA such as deacetylated HA (deHA), sulfated HA (sHA), and deacetylated and sulfated HA (s-deHA) were synthesized by modulating sulfating and deacetylating reagents to alter binding specificities to CD44. Modified HA derivatives and CD44 biophysical interactions were assessed by fluorescence polarization. In silico techniques were also used to determine binding using molecular docking and MM-PBSA approaches. …

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Identification Of More Potent And Efficacious Analogs Of The Novel Host-Derived Immunostimulant Ep67, Abdul Alshammari

Theses & Dissertations

EP67 is a human C5a-derived decapeptide agonist of C5a Receptor 1 (C5aR1/CD88) that selectively activates mononuclear phagocytes over neutrophils to stimulate protective innate and adaptive immune responses while potentially minimizing neutrophil-mediated toxicity. Two N-alkyl amino acids Pro⁷ and N-methyl-Leu⁸ (nme-Leu⁸) within EP67 induce structural changes that increase potency and selective activation of mononuclear phagocytes over neutrophils. Cis/trans isomerization at these positions, however, likely limits the activity of EP67 and low coupling efficiency between Pro⁷ and nme-Leu⁸ increases scale-up costs for clinical use. Thus, the goals of this study were to …

Computational Studies And Design Of Pparγ And Glut1 Inhibitors, Suliman Almahmoud

Theses & Dissertations

The peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor of the nuclear receptor superfamily that controls the expression of a variety of genes involved in fatty acid metabolism, adipogenesis, and insulin sensitivity. PPARγ is a target for insulin-sensitizing drugs, and it plays a significant function in prostate cancer. PPARγ antagonists have anti-proliferative effects in a broad range of hematopoietic and epithelial cell lines. The ligand binding domain (LBD) of PPARγ is large and has orthosteric and allosteric binding sites. Several PPARγ-ligand co-crystal structures show two bound molecules, one to the orthosteric pocket and a second to the allosteric …

The Development Of Novel Apurinic/Aprymidinic Endonuclease/Redox-Factor 1 Inhibitors For The Treatment Of Human Melanoma, Bella Sharifi

Pharmaceutical Sciences (MS) Theses

Apurinic/apyrimidinic DNA repair endonuclease-1 (APE1), first recognized as an important DNA excision repair enzyme, is also known as Redox Factor-1 (Ref-1) involved in the activation of many nuclear transcription factors in both redox-dependent and independent manner. It has been well-documented that the overexpression of APE/Ref-1 contributes to the development of chemo-resistance and is associated with tumor progression in many human malignancies [1].

Our previous study in melanoma demonstrated that the development of novel inhibitors targeting the redox regulation domain of APE/Ref-1 is a promising strategy for melanoma treatment. To date, limited successes have been reported in developing novel …

Amphiphilic Cell-Penetrating Hybrid Cyclic-Linear Peptides As A Drug Delivery System, Saghar Mozaffari

Pharmaceutical Sciences (PhD) Dissertations

A number of cyclic peptides containing a positively charged ring composed of arginine residues attached to hydrophobic tail made of tryptophan residues through a lysine linker namely [R₅K]W₅, [R₆K]W₅, [R₅K]W₆, [R₇K]W₅, [R₅K]W₇, [R₆K]W₆, and [R₇K]W₇ were synthesized and evaluated as molecular transporters. The peptides were evaluated for their ability to deliver, fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI), and fluorescent labeled anti-HIV drugs (F′-FTC and F′-d4T). The results indicated that the presence of positively …

After-Action Report: Tabletop Exercise On Opioid Crisis Response And Resilience, Alexander Siedschlag, Tiangeng Lu

Publications

AGENCY BRIEFINGS The opioid overdose epidemic has been characterized as the worst public health crisis in Pennsylvania, and the nation. Not only practitioners but also institutions of higher education with high research capacity, such as Penn State, are applying existing and developing new instruments to address opioid the crisis. Identifying best practices of preventing, protecting from, mitigating against, responding to, and recovering from opioid overdose outbreak is necessary for public health and safety and important for the overall homeland security enterprise, in consistency with the objectives of the Quadrennial Homeland Security Reviews (QHSR), the National Preparedness Goal (NPG), and the …

Synthesis Of Gadolinium-Doxorubicin Prodrug Carrying Functional Nanoceria For The Targeted Drug Delivery And Cancer Treatment, Arth Patel

Electronic Theses & Dissertations

The main focus of this research was the development of a polymer-coated nanoceria (PNC) platform to be used as a drug delivery system. Water-dispersible PNC is synthesized using a water-based alkaline precipitation method. Cerium nitrate hexahydrate and poly (acrylic acid) are used for the preparation of PNC. The synthesized PNC was characterized using ZETA, and UV- Vis characterization techniques. Polyacrylic acid (PAA)-coated cerium oxide nanoparticles fabricated for the targeted combination therapy of TNBC (MDA-MB-231) and MCF-7. Using EDC/NHS chemistry, the surface carboxylic acid groups of nanoceria was designed and synthesized with ICAM-1 antibody to target ICAM-1 overexpressing TNBC. Next, doxorubicin …

Subanesthetic Iv Ketamine Reduces Acute Suicidal Ideation In Patients With Mood Disorders, Kimberly Jenko, Jack Anzilotti

Physician Assistant Capstones, 2016 to 2019

Background. Depression and suicide are common in the United States and present a significant problem in the healthcare landscape. Currently, there are few options that can rapidly reduce suicidal ideation in patients with depression. Ketamine, a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to reduce acute suicidality in patients with depression. Previous studies have a reduction of suicidal ideation compared to saline placebo, but few studies have shown a significant effect compared to a similar psychoactive drug such as midazolam.

Method. A search of PubMed and PsychNET was performed in September 2018 using the terms “ketamine,” “suicide,” …

Gender Differences In Opioid Prescribing Patterns Among Adults In The Us, Salena Marie Preciado

Pharmaceutical Sciences (MS) Theses

This project aims to evaluate gender differences in opioid prescribing in ambulatory care and emergency department settings. The retrospective analysis of opioid prescribing rates in the US included all adult medical visits from 2006-2016. Data was collected from two nationally representative surveys, The National Ambulatory Medical Care Survey (NAMCS) and the National Hospital and Ambulatory Medical Care Survey (NHAMCS). Eligible patients were at least 18 years old on the date of the visit. Bivariate and multivariate analysis were used to identify factors associated with opioid prescribing.

Rates of opioid prescribing increased for both men and women over the study period. …

Impact Of Prevnar (Pcv13) Vaccine Recommendations In Pediatric And Immunocompetent Adults 65 Years And Older: What Are The Benefits And Risks?, James E. Watkins, Anne Marie Thibodeaux, John C. Darnell

Articles, Abstracts, and Reports

Background:

2000: PCV7 becomes the first FDA approved pneumococcal vaccine for pediatrics
2010: PCV13 recommended in pediatrics
2014: PCV13 recommended in immunocompetent adults 65+
2018: CDC looked at data since 2014 recommendation
2019: PCV13 now shared clinical decision-making

Non-Traditional Anti-Emetic Therapy For Cannabinoid Hyperemesis Syndrome: A Case Report, Sara Groome, Pharmd, Kelly Le, Pharmd, Christina Karalis, Pharmd, Eric Selvage, Pharmd, Brandi Thoma, Pharmd, Bcps, Bccp

Pharmacy Presentations, Posters, and Grand Rounds

• Marijuana is one of the most commonly utilized recreational drugs and is widely known for both its anti-emetic and appetite-stimulating properties
• Medicinal-grade marijuana has been available for patients suffering from various medical conditions, such as chemotherapy-induced nausea and vomiting, for example; it also has been utilized in patients with chronic pain, in addition to a number of other disease states
• While casual, intermittent use elucidates the aforementioned positive effects, chronic use of large quantities of marijuana may precipitate the contrary, such as extensive nausea and vomiting, a hallmark of Cannabinoid Hyperemesis Syndrome (CHS)
• CHS is hypothesized to result from alterations …

Does Dispensing Naloxone Kits To High-Risk Patients At The Time Of Emergency Department (Ed) Discharge Reduce The Burden Of Subsequent Overdose-Related Care?, Steven D. Perry, Charleen Gnisci, Rachel Beham

Emergency Medicine

Purpose: The rates of opioid-related overdose and death have remained at or near historically high levels despite reform in pharmaceutical opioid prescribing trends. This study will determine if a recently implemented protocol which aims to provide high-risk patients with naloxone emergency kits at the time of ED discharge has reduced the need for subsequent overdose-related care to a greater degree than providing the same patients with written outpatient naloxone prescriptions. Patients currently receive either intervention upon discharge from the ED based on a protocolized, criteria-based, provider-implemented decision-making tree that identifies patients at high risk for subsequent overdose.

Methods: This study …

Impact Of Required Antibiotic Stop Dates And Indications On Length Of Treatment In Hospitalized Patients With Pneumonia, Amanda Haddad, Kathryn Hernando, Kayihura Manigaba, Abigail Antigua

Infectious Disease

Purpose: The CDC Core Elements of Hospital Antibiotic Stewardship Programs recommends implementing policies to support optimal antibiotic prescribing including documentation of dose, duration and indication. On January 31, 2017, the study institution implemented new physician order entry screens in the electronic health record requiring the input of indication and duration on all antibiotic orders. The objective of this study is to determine if implementation of mandatory indication and duration for antibiotic orders decreases antibiotic duration of therapy in hospitalized patients with pneumonia.

Methods: This study was submitted to the Institutional Review Committee for approval. The clinical pharmacy surveillance platform, …

Pantoprazole Continuous Infusion Versus Intermittent Bolus For Gastrointestinal Bleed Prior To Esophagogastroduodenoscopy (Egd), Vy Dang Pharmd, Mickayla Clark Pharmd, Bcps, Kartika Shetty Md, James Hwang, Pinak Shah, Scott J. Anderson

Gastroenterology

Purpose: Practice guidelines recommend patients with non-variceal upper gastrointestinal (GI) bleeds who have a high risk of active bleeding, nonbleeding visible vessels, and adherent clots should be given proton pump inhibitors (PPIs) intravenous (IV) bolus followed by continuous infusion after esophagogastroduodenoscopy (EGD). The use of PPIs before EGD has shown to reduce the requirement for EGD, however, there are no studies evaluating the difference in outcomes of continuous infusion PPI versus intermittent IV bolus PPI prior to EGD. The objective of this study is to evaluate clinical outcomes of continuous infusion PPI versus intermittent IV bolus PPI prior to EGD. …

Utility Of Push Dose Vasopressor In The Emergency Department, Paul Nguyen, Daniel Giddings, Scott Dietrich, Kathryn Merkel

Emergency Medicine

Purpose: The purpose of this study is to evaluate push dose vasopressor (PDV) usage patterns, efficacy, and safety in a single community hospital emergency department when used for rapid sequence intubation (RSI). Pre-intubation hypotension is a positive correlator to incidences of cardiac arrest. Precautions should be in place to prevent and treat hypotension during emergent intubation. The emerging strategy of utilizing PDV in emergency department (ED) patients is an underexplored and potentially efficacious option.

Methods: This study will be submitted to the Institutional Review Board for approval. This retrospective evaluation will identify critically ill patients receiving phenylephrine or epinephrine PDV …

Retrospective Evaluation Of Hydromorphone Prescribing Patterns In The Emergency Department At A Community Hospital, Eduardo Martinez Sanchez, Winifred Pardo, Ada Jalice, James Adefisoye

All Publications

No abstract provided.