Medicine and Health Sciences Commons^™

Preparation And Evaluation Of Phospholipid-Based Complex Of Standardized Centella Extract (Sce) For The Enhanced Delivery Of Phytoconstituents, Suprit Saoji, Nishikant Raut, Pradip Dhore, Chandrashekhar D. Borkar, Michael Popielarczyk, Vivek S. Dave

Pharmacy Faculty/Staff Publications

In the present study, a phospholipid-based complex of standardized Centella extract (SCE) was developed with a goal of improving the bioavailability of its phytoconstituents. The SCE-phospholipid complex was prepared by solvent evaporation method and characterized for its physicochemical and functional properties. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), photomicroscopy, and powder x-ray diffraction (PXRD) were used to confirm the formation of Centella naturosome (CN). The prepared complex was functionally evaluated by apparent solubility, in vitro drug release, ex vivo permeation, and in vivo efficacy studies. The prepared CN exhibited a significantly higher (12-fold) aqueous …

A Phase I Study Of Ad5-Gucy2c-Padre In Stage I And Ii Colon Cancer Patients, Adam E. Snook, Trevor R. Baybutt, Michael J. Mastrangelo, Nancy L. Lewis, Scott D. Goldstein, Walter K. Kraft, Yaa D. Oppong, Terry Hyslop, Ronald E. Myers, Vitali Alexeev, Laurence C. Eisenlohr, Takami Sato, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Posters

Background

Ad5-GUCY2C-PADRE is a replication-deficient human type 5 recombinant adenovirus (Ad5) vaccine encoding guanylyl cyclase C (GUCY2C) fused to the PAn DR Epitope (PADRE). GUCY2C, a paracrine hormone receptor producing the second messenger cyclic GMP (cGMP), is selectively expressed by intestinal epithelial cells and a subset of hypothalamic neurons, but not other tissues. Importantly, GUCY2C is over-expressed in nearly all primary and metastatic human colorectal tumors. Preclinical studies in mice demonstrated selective tolerance of GUCY2C-specific CD4+ T cells, but not CD8+ T or B cells, necessitating inclusion of the exogenous CD4+ T helper cell epitope PADRE to maximize GUCY2C-specific CD8+ …

Design And Synthesis Of Novel Chloroquine-Based Antimalarials, Kevin Vincent Murphy

Dissertations and Theses

Malaria is an infectious, often fatal disease that afflicts nearly 200 million people every year. The disease, characterized by recurring and extreme flu-like symptoms, is caused by the protozoan parasite Plasmodium falciparum. Victims usually contract the disease through a mosquito vector. Chloroquine is a chemotherapeutic that was introduced in the 1940s. For many years the drug was the foremost treatment of malaria, being effective and producing few side effects. Unfortunately, tolerance to chloroquine developed when the parasite evolved a resistance mechanism. Newer drugs have been developed and implemented, but these medicines also show a decreasing effect with continued administration. …

High Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis, Chang-Guo Zhan, Fang Zheng, Wenchao Yang

Pharmaceutical Sciences Faculty Patents

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (-)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (-)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

Pharmacology: The Pharmacodynamics Of Nutrients And Nutrient Interactions In Biological Functions, M. Hasan Mohajeri, Gunter P. Eckert, James R. Pauly, Christopher M. Butt

Pharmaceutical Sciences Faculty Publications

No abstract provided.

Cysteine And Arginine-Rich Peptides As Molecular Carriers, Amir Nasrolahi Shirazi, Naglaa Salem El-Sayed, Dindayal Mandal, Rakesh Tiwari, Kathy Tavakoli, Matthew Eteshem, Keykavous Parang

Pharmacy Faculty Articles and Research

A number of linear and cyclic peptides containing alternative arginine and cysteine residues, namely linear (CR)₃, linear (CR)₄, linear (CR)_5, cyclic [CR]₄, and cyclic [CR]₅, were synthesized. The peptides were evaluated for their ability to deliver two molecular cargos, fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI) and fluorescence-labeled lamivudine (F′-3TC), intracellularly in human leukemia cancer (CCRF-CEM) cells. We investigated the role of cyclization and the number of amino acids in improving the transporting ability of the peptides. The flow cytometry studies suggested that the synthesized peptides were able to work efficiently as …

Regulating Drug Promotion To Promote The Public Health: A Response To Bennett, Et Al., Patricia J. Zettler

Faculty Publications By Year

No abstract provided.

A Novel Approach To Identify Shared Fragments In Drugs And Natural Products, Ashkay Balasubramanya, Ishwor Thapa, Dhundy Raj Bastola, Dario Ghersi

Interdisciplinary Informatics Faculty Proceedings & Presentations

Fragment-based approaches have now become an important component of the drug discovery process. At the same time, pharmaceutical chemists are more often turning to the natural world and its extremely large and diverse collection of natural compounds to discover new leads that can potentially be turned into drugs. In this study we introduce and discuss a computational pipeline to automatically extract statistically overrepresented chemical fragments in therapeutic classes, and search for similar fragments in a large database of natural products. By systematically identifying enriched fragments in therapeutic groups, we are able to extract and focus on few fragments that are …

Discovery Of Novel Tubulin Polymerization Inhibitors And Survivin Inhibitors As Potential Anticancer Agents, Min Xiao

Theses and Dissertations (ETD)

Melanoma is the most dangerous form of skin cancer and accounts for the majority of skin cancer death. Although considerable advances have been made in melanoma treatment in recent years, there are many problems associated with current therapies. Drug resistance to targeted therapies is almost inevitable after short term treatment. Immunotherapies generally have low response rate and the effects vary among patients. Therefore, the need to develop new and more effective treatment for melanoma is high.

The work presented here focuses on discovery of novel anticancer agents for melanoma by targeting two important cancer targets: tubulin and survivin. Microtubules play …

Challenges In The Pharmacokinetics Of Therapeutic Proteins, Wararat Limothai

Theses and Dissertations (ETD)

Due to the complex structure and complicated disposition pattern of therapeutic macromolecules, their pharmacokinetic interpretation has many challenges. Two of these challenges were investigated in this dissertation: 1) the error of classical bioavailability assessment observed during subcutaneous (SC) administration of therapeutic macromolecules that undergo target-mediated drug disposition (TMDD) and 2) the ontogeny of the neonatal Fc receptor (FcRn) expression along with its effect on the pharmacokinetics of monoclonal antibodies (mAbs) during development.

TMDD often well describes the pharmacokinetics of therapeutic proteins that have high specificity and affinity of binding to their target receptors. The target receptors can be saturated by …

Apobec3g Interacts With Ssdna By Two Modes: Afm Studies., Luda S. Shlyakhtenko, Samrat Dutta, Jaspreet Banga, Ming Li, Reuben S. Harris, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

APOBEC3G (A3G) protein has antiviral activity against HIV and other pathogenic retroviruses. A3G has two domains: a catalytic C-terminal domain (CTD) that deaminates cytidine, and a N-terminal domain (NTD) that binds to ssDNA. Although abundant information exists about the biological activities of A3G protein, the interplay between sequence specific deaminase activity and A3G binding to ssDNA remains controversial. We used the topographic imaging and force spectroscopy modalities of Atomic Force Spectroscopy (AFM) to characterize the interaction of A3G protein with deaminase specific and nonspecific ssDNA substrates. AFM imaging demonstrated that A3G has elevated affinity for deaminase specific ssDNA than for …

Structural Characterization Of Cals8, A Tdp-Α-D-Glucose Dehydrogenase Involved In Calicheamicin Aminodideoxypentose Biosynthesis, Shanteri Singh, Karolina Michalska, Lance Bigelow, Michael Endres, Madan K. Kharel, Gyorgy Babnigg, Ragothaman M. Yennamalli, Craig A. Bingman, Andrzej Joachimiak, Jon S. Thorson, George N. Phillips Jr.

Center for Pharmaceutical Research and Innovation Faculty Publications

Classical UDP-glucose 6-dehydrogenases (UGDHs; EC 1.1.1.22) catalyze the conversion of UDP-α-d-glucose (UDP-Glc) to the key metabolic precursor UDP-α-d-glucuronic acid (UDP-GlcA) and display specificity for UDP-Glc. The fundamental biochemical and structural study of the UGDH homolog CalS8 encoded by the calicheamicin biosynthetic gene is reported and represents one of the first studies of a UGDH homolog involved in secondary metabolism. The corresponding biochemical characterization of CalS8 reveals CalS8 as one of the first characterized base-permissive UGDH homologs with a >15-fold preference for TDP-Glc over UDP-Glc. The corresponding structure elucidations of apo-CalS8 and the CalS8·substrate·cofactor ternary complex (at 2.47 and 1.95 Å …

Ethanol Pharmacokinetics In Neonates Secondary To Medication Administration, Elizabeth Marek, Pharmd, Susan C. Adeniyi-Jones, Md, Lindsey Roke, Pharmd, Tara E. Decerbo, Pharmd, Rebecca L. Cordell, Pharmd, Paul S. Monks, Pharmd, Walter K. Kraft, Md

Department of Pharmacology and Experimental Therapeutics Posters

Purpose:

Ethanol serves as a solvent and microbial preservative in oral liquid medications and is the second most commonly used solvent in liquid medications following water. Despite widespread use of ethanol in liquid medications for neonates, the pharmacokinetics and toxicity of ethanol in young children are not well described. The aim of the current study is to quantify blood ethanol levels in neonates secondary to oral ethanol containing medications.

Methods:

Neonates who received either oral phenobarbital (15% ethanol) and/or oral dexamethasone (30% ethanol) per standard of care were eligible for enrollment. A maximum of 6 blood samples per patient (4.5 …

An In Vitro Assessment Of Liposomal Topotecan Simulating Metronomic Chemotherapy In Combination With Radiation In Tumor-Endothelial Spheroids, Amar Jyoti, Kyle Daniel Fugit, Pallavi Sethi, Ronald C. Mcgarry, Bradley D. Anderson, Meenakshi Upreti

Pharmaceutical Sciences Faculty Publications

Low dose metronomic chemotherapy (LDMC) refers to prolonged administration of low dose chemotherapy designed to minimize toxicity and target the tumor endothelium, causing tumor growth inhibition. Topotecan (TPT) when administered at its maximum tolerated dose (MTD) is often associated with systemic hematological toxicities. Liposomal encapsulation of TPT enhances efficacy by shielding it from systemic clearance, allowing greater uptake and extended tissue exposure in tumors. Extended release of TPT from liposomal formulations also has the potential to mimic metronomic therapies with fewer treatments. Here we investigate potential toxicities of equivalent doses of free and actively loaded liposomal TPT (LTPT) and compare …

Use Of Tris-Quaternary Ammonium Salts As Pain Modulating Agents, Joseph R. Holtman, Peter Anthony Crooks, Linda P. Dwoskin, J. Michael Mcintosh

Pharmaceutical Sciences Faculty Patents

Provided are tris-quatemary ammonium compounds which are modulators of nociception and pain.

The Flaws And Human Harms Of Animal Experimentation, Aysha Akhtar

Experimentation Collection

Nonhuman animal (“animal”) experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal …

Selective C1 Lesioning Slightly Decreases Angiotensin Ii Type I Receptor Expression In The Rat Rostral Ventrolateral Medulla (Rvlm)., Erick A Bourassa, Kristen A Stedenfeld, Alan F Sved, Robert Charles Speth

Faculty Articles

Cardiovascular homeostasis is regulated in large part by the rostral ventrolateral medulla (RVLM) in mammals. Projections from the RVLM to the intermediolateral column of the thoracolumbar spinal cord innervate preganglionic neurons of the sympathetic nervous system causing elevation of blood pressure and heart rate. A large proportion, but not all, of the neurons in the RVLM contain the enzymes necessary for the production of epinephrine and are identified as the C1 cell group. Angiotensin II (Ang II) activates the RVLM acting upon AT1 receptors. To assess the proportion of AT1 receptors that are located on C1 neurons in the rat …

Nsu Sharks Rx - Fall 2015, College Of Pharmacy

NSU Sharks Rx

No abstract provided.

A Solid Dispersion Based On Milk-Micelle As A Drug-Carrier For The Enhancement Of The Aqueous Solubility Of Ritonavir, Pradip Dhore, Suprit Saoji, Nishikant Raut, M. Bernardez, Rahul V. Haware, Vivek S. Dave

Pharmacy Faculty/Staff Publications

The goal of present investigation was to evaluate the feasibility of formulating a solid-dispersion using milk-micelles as drug-carriers, to enhance the aqueous solubility of ritonavir.

The Enhancement Of The Aqueous Solubility Of Ritonavir Via Formulation Of A Drug-Phospholipid Complex, Suprit Saoji, Nishikant Raut, Pradip Dhore, R. G. Diware, M. Bernardez, Rahul V. Haware, Vivek S. Dave

Pharmacy Faculty/Staff Publications

Objective: To evaluate the enhancement of aqueous solubility of a poorly water soluble drug ritonavir by forming its complex with a phospholipid (Phospholipon®90H).

Formulation Of A Drug-Phospholipid Complex (Naturosome) To Enhance The Aqueous Solubility Of Standardized Extract Of Centella Asiastica (Sce), Suprit Saoji, Nishikant Raut, Pradip Dhore, M. Bernardez, Rahul V. Haware, Vivek S. Dave

Pharmacy Faculty/Staff Publications

Purpose:

To evaluate the enhancement of aqueous solubility of standardized extract of Centella asiastica, a natural drug with known anti- Alzheimer’s activity, by formulating its complex (Naturosome) with a phospholipid - Phospholipon® 90H.

Pharmdigest Volume 2, Issue 1, Philadelphia College Of Osteopathic Medicine, School Of Pharmacy

PharmDigest

This issue of the Pharmacy Student Council newsletter includes the following articles:

• Greetings
• What is Your King Piece?
• Economics in Pharmacy
• Community Pharmacy
• The Daily Dose: APhA in D.C.
• GSHP Summer Meeting
• Tips for Students
• Pharmacy goes Greek
• A Trip to Philly
• Institutional Pharmacy
• Message to the P1s

Monitoring Of Outpatient Parenteral Antimicrobial Therapy (Opat) And Implementation Of Clinical Pharmacy Services At A Community Hospital Infusion Unit, Punit J. Shah, Scott Bergman, Donald Graham, Stephanie Glenn

SIUE Faculty Research, Scholarship, and Creative Activity

Background: In 2004, the Infectious Diseases Society of America (IDSA) published monitoring guidelines for outpatient parenteral antimicrobial therapy (OPAT), but no assessment of their utilization has been reported. We evaluated adherence to these recommendations by physicians at infusion centers and then piloted a program of supervision of monitoring by pharmacists.

Methods: Phase I: We performed a retrospective case-control study of patients who received OPAT over one year at two hospital infusion centers. Controls were patients treated by an infectious diseases (ID) physician, and cases were those without an ID physician. Patients were excluded if they received fewer than …

Copd: Optimizing Treatment, Nabila Ahmed-Sarwar, Deirdre P. Pierce, David C. Holub

Pharmacy Faculty/Staff Publications

A guideline update and an expanded armamentarium have many physicians wondering how best to treat patients with COPD. Chronic obstructive pulmonary disease (COPD) carries a high disease burden. In 2012, it was the 4th leading cause of death worldwide.1,2 In 2015, the World Health Organization updated its Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, classifying patients with COPD based on disease burden as determined by symptoms, airflow obstruction, and exacerbation history.3 These revisions, coupled with expanded therapeutic options within established classes of medications and new combination drugs to treat COPD (TABLE 1),3-6 have led to questions about interclass …

Silver Nanoparticles Induce Tight Junction Disruption And Astrocyte Neurotoxicity In A Rat Blood-Brain Barrier Primary Triple Coculture Model, Liming Xu, Mo Dan, Anliang Shao, Xiang Cheng, Cuiping Zhang, Robert A. Yokel, Taro Takemura, Nobutaka Hanagata, Masami Niwa, Daisuke Watanabe

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Silver nanoparticles (Ag-NPs) can enter the brain and induce neurotoxicity. However, the toxicity of Ag-NPs on the blood-brain barrier (BBB) and the underlying mechanism(s) of action on the BBB and the brain are not well understood.

METHOD: To investigate Ag-NP suspension (Ag-NPS)-induced toxicity, a triple coculture BBB model of rat brain microvascular endothelial cells, pericytes, and astrocytes was established. The BBB permeability and tight junction protein expression in response to Ag-NPS, NP-released Ag ions, and polystyrene-NP exposure were investigated. Ultrastructural changes of the microvascular endothelial cells, pericytes, and astrocytes were observed using transmission electron microscopy (TEM). Global gene expression …

Compatibility Of Vancomycin And Oxacillin During Simulated Y-Site Delivery, Chad A. Knoderer, Hilary M. Teibel, Kristen R. Nichols

Scholarship and Professional Work – COPHS

Background: Vancomycin and oxacillin may be used together as empiric coverage in patients with proven or suspected Staphylococcus aureus infections. Though vancomycin hydrochloride 20 mg/mL and oxacillin sodium 160 mg/mL are reported to be compatible via Y-site delivery, Y-site compatibility of commonly used concentrations, vancomycin 10 mg/mL and oxacillin 20 mg/mL, has not yet been reported. Objective: To determine the Y-site compatibility of vancomycin 10 mg/mL and oxacillin 20 mg/mL. Methods: One vancomycin hydrochloride 1 g vial was reconstituted with 10 mL sterile water for injection (SWFI) and diluted with 90 mL 5% dextrose in water (D5W) …

Stilbene Analogs And Methods Of Treating Cancer, David Watt, Chunming Liu, Vitaliy M. Sviripa, Wen Zhang

Pharmaceutical Sciences Faculty Patents

Stilbene analogs and pharmaceutical compositions that are useful for the treatment of various cancers, including without limitation, colorectal cancer (CRC) and breast cancer are disclosed. The halogenated stilbene analogs include nitrogen heteroaryl groups and/or amino groups on the stilbene ring.

Ebola Virus Infection: Overview And Update On Prevention And Treatment, Miguel J. Martínez, Abdulbaset M. Salim, Juan C. Hurtado, Paul E. Kilgore

Department of Pharmacy Practice

In 2014 and 2015, the largest Ebola virus disease (EVD) outbreak in history affected large populations across West Africa. The goal of this report is to provide an update on the epidemic and review current progress in the development, evaluation and deployment of prevention and treatment strategies for EVD. Relevant information was identified through a comprehensive literature search using Medline, PubMed and CINAHL Complete and using the search terms Ebola, Ebola virus disease, Ebola hemorrhagic fever, West Africa outbreak, Ebola transmission, Ebola symptoms and signs, Ebola diagnosis, Ebola treatment, vaccines for Ebola and clinical trials on Ebola. Through 22 July …

A Perspective On Pharmaceutical Marketing Practices: Message Development, Media Selection, Medication Adherence And Health Literacy, Yvette L. Bonaparte

Atlantic Marketing Association Proceedings

According to the National Action Plan to Improve Health Literacy issued in 2010 by the U.S. Department of Health and Human Services, health literacy is a multi-faceted concept and has importance for multiple sectors. Stakeholders typically involved in the health literacy discussion include government, public health officials, practitioners and those concerned with health promotion (U.S. Department of Health and Human Services 2010). In addition to these stakeholders, there is the opportunity for the pharmaceutical industry to be an active participant in the health literacy discussion.

Given the variation in health literacy levels among the U.S. population and the impact of …

Magic Bullet, Karen Haydock

The Transdisciplinary STEAM+ Journal

Two of the most powerful types of corporations in the world today are those that produce pharmaceuticals and weapons. While the corporations are concerned with increasing their profits, we wonder if their products have any magical powers.

[India ink on rag paper]

This poster explores the military-industrial complex. The weapons industry profits through imperialism. The pharmaceutical industry profits through by taking advantage of people’s illnesses.

The poster has multiple interpretations, hopefully encouraging the viewer to participate by asking relevant questions, such as:

“What is that person drinking?”

”Are they pills or bombs?”

“Medicines cure us - how can a pill …