Pharmacy and Pharmaceutical Sciences Commons^™

Comparative Studies Between The Murine Immortalized Brain Endothelial Cell Line (Bend.3) And Induced Pluripotent Stem Cell-Derived Human Brain Endothelial Cells For Paracellular Transport, Jiahong Sun, Weijun Ou, Derick Han, Annlia Paganini-Hill, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Brain microvascular endothelial cells, forming the anatomical site of the blood-brain barrier (BBB), are widely used as in vitro complements to in vivo BBB studies. Among the immortalized cells used as in vitro BBB models, the murine-derived bEnd.3 cells offer culturing consistency and low cost and are well characterized for functional and transport assays, but result in low transendothelial electrical resistance (TEER). Human-induced pluripotent stem cells differentiated into brain microvascular endothelial cells (ihBMECs) have superior barrier properties, but the process of differentiation is time-consuming and can result in mixed endothelial-epithelial gene expression. Here we performed a side-by-side comparison of the …

A Single Local Delivery Of Paclitaxel And Nucleic Acids Via An Immunoactive Polymer Eliminates Tumors And Induces Antitumor Immunity, Fanfei Meng, Jianping Wang, Yanying He, Gregory M. Cresswell, Nadia A. Lanman, L. Tiffany Lyle, Timothy L. Ratliff, Yoon Yeo

Purdue University Libraries Open Access Publishing Fund

Despite recent advances in cancer therapy, hard-to-reach, unidentified tumors remain a significant clinical challenge. A promising approach is to treat locatable and accessible tumors locally and stimulate antitumor immunity in situ to exert systemic effects against distant tumors. We hypothesize that a carrier of immunotherapeutics can play a critical role in activating antitumor immunity as an immunoadjuvant and a local retainer of drug combinations. Here, we develop a polyethyleneimine-lithocholic acid conjugate (2E′), which forms a hydrophobic core and cationic surface to codeliver hydrophobic small molecules and anionic nucleic acids and activates antigen-presenting cells via the intrinsic activities of 2E′ components. …

Development Of Anti-Inflammatory Theranostic Nanocolloids Using Quality By Design Approaches, Michele Herneisey

Electronic Theses and Dissertations

Nanocolloids are attractive delivery vehicles for drugs with poor aqueous solubility. Despite this, relatively few nanocolloid products exist on the market. Currently, there is a lack of standardization in the pre-clinical, academic setting regarding nanocolloid development and quality control testing. Adaptation of quality by design (QbD) methods used in the pharmaceutical industry to nanocolloid development is a desirable approach that can improve nanocolloid product and process understanding, resulting in an increased number of marketable products.

The central hypothesis of this work is that QbD approaches can be utilized to optimize theranostic (therapeutic and diagnostic) nanocolloid stability, drug loading, and imaging …

Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice. Though the methods for Aβ detection and quantification have been well established and documented, the impact of the size of the …

American Association Of Colleges Of Pharmacy (Aacp) Co-Curriculum Toolkit, Abir Kanaan, Andrea Mekonnen, April Staton, Cameron C. Lindsey, Dave Weldon, Farid G. Khalafalla, Jaime Maerten-Rivera, Kelly Shields, Lara Gomez, Laressa Bethishou, Maria Thurston, Mike Fulford, Nandita Das, Priti Patel, Rebecca Kavanagh, Stacey Olstad, Zachary Jenkins

Pharmacy Faculty Articles and Research

"The co-curriculum is intended to run parallel to the formal curriculum and support the development of students’ professional knowledge, skills, abilities, behaviors, and attitudes, including scientific foundation, knowledge application, and practice competencies. Additionally, the co-curriculum can also support proficiency in skills and achievement of competencies that are concurrently taught within the formal curriculum. ACPE evaluates the way programs assess students’ acquisition of knowledge and application of knowledge to practice within co-curricular experiences and especially how they advance the professional development of students within affective domain areas of learning."

Will Reducing Drug Prices Slow Innovation?, Gregory Vaughan, Fred Ledley

Mathematical Sciences Faculty Publications

The pharmaceutical industry has long argued that high drug prices reflect the high cost of innovation and that reducing drug prices would necessarily slow the pipeline of new drugs. These arguments have been bolstered by studies of large pharmaceutical companies showing statistical associations between the projected market size or revenue for pharmaceutical products and research & development (R&D) activity. Our analysis recognizes the increasingly important role of small biopharmaceuticals in drug development , companies that typically have little revenue and negative earnings, but are now responsible for more than 40% of new drug approvals. We examine the relationship between changes …

Will Reducing Drug Prices Slow Innovation?, Gregory Vaughan, Fred Ledley

Natural & Applied Sciences Faculty Publications

The pharmaceutical industry has long argued that high drug prices reflect the high cost of innovation and that reducing drug prices would necessarily slow the pipeline of new drugs. These arguments have been bolstered by studies of large pharmaceutical companies showing statistical associations between the projected market size or revenue for pharmaceutical products and research & development (R&D) activity. Our analysis recognizes the increasingly important role of small biopharmaceuticals in drug development , companies that typically have little revenue and negative earnings, but are now responsible for more than 40% of new drug approvals. We examine the relationship between changes …

Cerium Dioxide, A Jekyll And Hyde Nanomaterial, Can Increase Basal And Decrease Elevated Inflammation And Oxidative Stress, Robert Yokel, Marsha L. Ensor, Hemendra J. Vekaria, Patrick G. Sullivan, David J. Feola, Arnold Stromberg, Michael T. Tseng, Douglas A. Harrison

Pharmaceutical Sciences Faculty Publications

It was hypothesized that the catalyst nanoceria can increase oxidative

stress/inflammation from the basal state and reduce it from the elevated state .

Nanoceria are cleared by macrophages. To test the hypothesis, M0 (non-polarized),

M1- (classically activated, pro-inflammatory), and M2-like (alternatively activated,

regulatory phenotype) RAW 264.7 macrophages were nanoceria exposed. Responses

were quantified by arginase activity, IL-1ß level, cell oxygen consumption rate (OCR),

the glycolysis stress test (GST), morphology determined by light microscopy,

macrophage phenotype marker expression and morphology using a novel three

dimensional immunohistochemical method, and RT-qPCR. Nanoceria blocked

arginase and IL-1ß effects, increased M0 cell OCR and GST …

Effectiveness And Safety Of Oral Anticoagulants In Non-Valvular Atrial Fibrillation Patients With Prior Bleeding Events: A Retrospective Analysis Of Administrative Claims Databases, G. Y. H. Lip, Allison V. Keshishian, Amiee Kang, Xuemei Luo, Nipun Atreja, Yan Zhang, Patricia Schuler, Jenny Jiang, Huseyin Yuce, Steve Deitelzweig

Publications and Research

Introduction

There are a paucity of real-world data examining effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in nonvalvular atrial fibrillation (NVAF) patients with prior bleeding.

Methods

This retrospective analysis included data from 5 insurance claims databases and included NVAF patients prescribed OACs with prior bleeding. One-to-one propensity score matching was conducted between NOACs and warfarin and between NOACs in each database. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and MB.

Results

A total of 244,563 patients (mean age 77; 50% female) with prior bleeding included 55,094 (22.5%) treated …

Updates In The Pharmacologic Prophylaxis And Treatment Of Invasive Candidiasis In The Pediatric And Neonatal Intensive Care Units, James Hunter Fly, Seerat Kapoor, Kelly Bobo, Jeremy S. Stultz

Faculty Publications

Purpose of review The goal of this review was to provide an update on the prevention and treatment options for invasive candidiasis (IC) in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU).

Recent findings Studies have further validated the use of fluconazole for IC prophylaxis among high-risk patients in the NICU. It remains unclear if prophylaxis leads to resistance development and the ideal dosage regimen is still not clear. Recent studies have been published comparing caspofungin and micafungin to amphotericin B and illustrated similar efficacy outcomes in the NICU. Micafungin now has approval from the United …

The Use Of Silica Nanoparticles For Controlled Drug Delivery Of Nicotine, Jennifer C. Iwenofu

Honors College Theses

Drug molecules can be administered in different ways to the human body. Nanotechnology stands out over other alternatives by delivering drugs to specific locations and reducing reactivity time. In this research, the hydrogen bond between silica nanoparticles and the drug molecule, nicotine, were studied to controllably deliver nicotine by varying pH values.

Cytotoxic Activity Of Non-Specific Lipid Transfer Protein (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Saud O. Alshammari, Taibah Aldakhil, Qamar A. Alshammari, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Trachyspermum ammi, commonly known as Ajwain, is a member of the Apiaceae family. It is a therapeutic herbal spice with diverse pharmacological properties, used in traditional medicine for various ailments. However, all previous studies were conducted using small molecule extracts, leaving the protein’s bioactivity undiscovered.

Aim

The current study aimed to demonstrate the cytotoxic activity of Ajwain non-specific lipid transfer protein (nsLTP1) in normal breast (MCF10A), breast cancer (MCF-7), and pancreatic cancer (AsPC-1) cell lines. Also, to evaluate its structural stability in human serum as well as at high temperature conditions.

Methods

The cytotoxic activity of Ajwain nsLTP1 was …

The Development Of A Brain Penetrating Erythropoietin For The Treatment Of Alzheimer’S Disease, Joshua Yang

KGI Theses and Dissertations

The development of a neurotherapeutic for the treatment of Alzheimer’s Disease (AD) is challenging due to limited endpoint efficacy. Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for AD but has limited blood-brain barrier (BBB) permeability. A chimeric fusion protein of EPO bound to the transferrin receptor monoclonal antibody (cTfRMAb) can act as a molecular trojan horse for brain drug delivery, shuttling EPO into the brain via the transvascular route. However, cTfRMAbs have Fc-effector function adverse effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly (cTfRMAb-N292G-EPO) reduces this Fc effector function. Hence, developing this …

A Small Peptide Increases Drug Delivery In Human Melanoma Cells, Shirley Tong, Shaban Darwish, Hanieh Hossein Nejad Ariani, Kate Alison Lozada, David Salehi, Maris A. Cinelli, Richard B. Silverman, Kamaljit Kaur, Sun Yang

Pharmacy Faculty Articles and Research

Melanoma is the most fatal type of skin cancer and is notoriously resistant to chemotherapies. The response of melanoma to current treatments is difficult to predict. To combat these challenges, in this study, we utilize a small peptide to increase drug delivery to melanoma cells. A peptide library array was designed and screened using a peptide array-whole cell binding assay, which identified KK-11 as a novel human melanoma-targeting peptide. The peptide and its D-amino acid substituted analogue (VPWxEPAYQrFL or D-aa KK-11) were synthesized via a solid-phase strategy. Further studies using FITC-labeled KK-11 demonstrated dose-dependent uptake in human melanoma cells. D-aa …

Evaluation Of Anemia In Communities Served By Shoulder To Shoulder Global: A Cross-Sectional Study In Santo Domingo, Ecuador, Kevin J. Mercer, Daniela Claudia Moga, Steven Fleming, Cristian Carrión, Melody Ryan

Pharmacy Practice and Science Faculty Publications

Background Shoulder to Shoulder Global (STSG) recognizes anemia as a cause of morbidity among patients in Santo Domingo, Ecuador. Little research has been done to assess targetable anemia risk factors to serve as a foundation for future pharmacotherapeutic interventions. This study sought to characterize anemia in this population to lay the foundation for future preventive intervention.

Methods Cross-sectional data obtained from existing clinic records from 2010 to 2016 included hemoglobin/hematocrit, age, sex, pregnancy status, and respective community. Chi-square compared means to examine risk factors associated with anemia. Logistic regression and odds ratios (OR) were used to estimate risk factors associated …

Tungsten-Enhanced Breast Cancer Metastasis To The Bone Is Associated With Alterations In The Bone Niche., Cameron J. Chock, Alicia Bolt

Pharmaceutical Sciences ETDs

The objective of this thesis project was to investigate the effects of tungsten on breast cancer metastasis to the bone niche, using the 4T1 orthotopic breast cancer model. Oral tungsten (15 ppm) exposure did not affect primary tumor growth. However, following tungsten exposure there were marked changes in the bone niche, including increased metastasis of 4T1 tumor cells and increased osteolysis. Further analysis of the bone niche indicates that enhanced metastasis is associated with a pro-tumorigenic immune suppressive environment, including increased number of granulocytic myeloid derived suppressor cells and increased gene expression of the pro-inflammatory cytokine IL-1β and the activated …

Isolation Of Sphingolipids From Sphingomonas Echinoides B-3126 And Their Characterization By Ms/Ms Analysis, Edgar David Uribe Sanchez

Honors Theses

EDGAR DAVID URIBE SANCHEZ: Isolation of Sphingolipids from Sphingomonas echinoides B-3126 and their Characterization by MS/MS Analysis

Sphingolipids are important components in human cellular lipid membranes and are differentiated by the incorporation of serine with an amide bond between the amino acid and a lipid tail. Sphingolipids produced by bacteria differ in both headgroups attached to the serine alcohol and the architecture of the lipid backbone. While the synthesis of sphingolipids in mammalian cells is well studied, only a handful of steps in the pathway are described in bacteria.¹ The observations that although sphingolipid synthesis is rare in bacteria, …

The Synthesis And Characterization Of Ionic Liquids Using Nitrogen-Based Cations For Transdermal Delivery, Jo Galloway

Honors Theses

The purpose of this research was to explore the synthesis mechanisms of water-soluble ionic liquids with nitrogen-containing cationic bases for future use in transdermal drug delivery and forensic science applications. Ionic liquids are salts with an organic cation and either an organic or inorganic anion. They have asymmetric structures, which means that the molecules don’t pack together as neatly as other salts do, therefore, they don’t crystallize as easily, and their melting points are lower. Ionic liquids have melting points below 100°C, and many are liquid at room temperature. Mechanistic studies reveal that the potency of ILs in enhancing transdermal …

Biologically-Inspired Nanoparticles For Oncology Applications, Aishwarya Bapat

Theses & Dissertations

Cancer is the leading cause of death in the United States and its high mortality rate can be attributed towards poor diagnosis methods and less effective therapeutic treatments. Many nanotechnology-based diagnostics and therapeutics are being developed to improve cancer patient outcomes. In this work, we have studied nanoparticles for diagnostic and therapeutic applications in cancer treatment.

In the first work, novel fluorescent NPs loaded with indocyanine green (ICG) were developed for bioimaging applications of pancreatic cancer. Targeted fluorescent nanoparticles (NPs) are being developed to image a range of cancer types with the goal to improve patient outcomes by utilizing in …

The Development Of Thermoresponsive Hydrogel-Based Drug Delivery Systems For The Treatment Of Musculoskeletal Diseases, Ningrong Chen

Theses & Dissertations

Water-soluble polymers are one of the most commonly used drug delivery vehicles for musculoskeletal diseases. During the past few decades, various biocompatible polymers have been employed in the development of thermoresponsive hydrogels as drug delivery systems for the treatment of local musculoskeletal pathologies. As part of our laboratory’s contribution to this field of study, I have successfully developed three thermoresponsive hydrogel-based formulations for the treatment of three different pathologies associated with the musculoskeletal system.

As my initial effort, I have developed a bone-targeting injectable hydrogel drug delivery system based on Pluronic 127 (Poloxamer 407), which is a Generally Recognized As …