Medicinal and Pharmaceutical Chemistry Commons^™

Formulation And In Vivo Evaluation Of Aliskiren-Loaded Poly(Lactic-Co-Glycolic) Acid Nanoparticles, Derek E. Murrell, Jessica M. Coleman, Stacy D. Brown, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Aliskiren (ALS) is a direct renin inhibitor with low bioavailability and high drug cost. The goal of this study was to increase the bioavailability of ALS through nanoformulation. The optimized formulation was then evaluated in spontaneously hypertensive rats (SHRs). We developed an ALS poly(lactic-co-glycolic) acid nanoparticle (ALS-NP) through the emulsion–diffusion–evaporation method with various solvents, stabilizer concentrations, and centrifugation speeds. SHRs were orally dosed with 30 mg/kg ALS or dose equivalent ALS-NP. Several parameters were assayed in plasma and/or urine at baseline and 24 h post-dose, while pharmacokinetic analysis included serial sampling. The optimum formulation was found with ethyl acetate, a …

Low And Moderate Prenatal Ethanol Exposure Of Mice During Gastrulation Or Neurulation Delays Neurobehavioral Development, Uta B. Schambra, Jeff Goldsmith, Kevin Nunley, Yali Liu, Sam Harirforoosh, Heidi M. Schambra

Pharmacy Faculty Articles and Research

Human and animal studies show significant delays in neurobehavioral development in offspring after prolonged prenatal exposure to moderate and high ethanol doses resulting in high blood alcohol concentration (BECs). However, none have investigated the effects of lower ethanol doses given acutely during specific developmental time periods. Here, we sought to create a mouse model for modest and circumscribed human drinking during the 3rd and 4th weeks of pregnancy.

We acutely treated mice during embryo gastrulation on gestational day (GD) 7 or neurulation on GD8 with a low or moderate ethanol dose given via gavage that resulted in BECs of 107 …

Effects Of Pringle Maneuver And Partial Hepatectomy On The Pharmacokinetics And Blood–Brain Barrier Permeability Of Sodium Fluorescein In Rats, Mohammad K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Liver diseases are known to affect the function of remote organs. The aim of the present study was to investigate the effects of Pringle maneuver, which results in hepatic ischemia–reperfusion (IR) injury, and partial hepatectomy (Hx) on the pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a widely used marker of blood–brain barrier (BBB) permeability. Rats were subjected to Pringle maneuver (total hepatic ischemia) for 20 min with (HxIR) or without (IR) 70% hepatectomy. Sham-operated animals underwent laparotomy only. After 15 min or 8 h of reperfusion, a single 25-mg/kg dose of FL was injected intravenously and serial …

Haemophilus Influenzae Responds To Glucocorticoids Used In Asthma Therapy By Modulation Of Biofilm Formation And Antibiotic Resistance, Chris S. Earl, Tee Wooi Keong, Shi-Qi An, Sarah Murdoch, Yvonne Mccarthy, Junkal Garmendia, Joseph Ward, J Maxwell Dow, Liang Yang, George A. O'Toole, Robert P. Ryan

Dartmouth Scholarship

Glucocorticosteroids are used as a main treatment to reduce airway inflammation in people with asthma who suffer from neutrophilic airway inflammation, a condition frequently associ- ated with Haemophilus influenzae colonization. Here we show that glucocorticosteroids have a direct influence on the behavior of H. influenzae that may account for associated difficulties with therapy. Using a mouse model of infection, we show that cortico- steroid treatment promotes H. influenzae persistence. Transcrip- tomic analysis of bacteria either isolated from infected mouse airway or grown in laboratory medium identified a number of genes encoding regulatory factors whose expression responded to the presence of …

Custom Fluorophores For Investigating The Cellular Uptake Mechanisms And Side-Effects Of Pharmaceuticals, Yu-Hsuan Chu

Dissertations and Theses

There is a significant current need to elucidate the molecular mechanisms of the side-effects caused by widely-used pharmaceuticals. Examples include the acute nephrotoxicity and irreversible ototoxicity promoted by the cationic drugs gentamicin and cisplatin. Gentamicin is an aminoglycoside antibiotic used for the prevention and treatment of life-threatening gram-negative bacterial infections, such as tuberculosis and meningitis. Cisplatin is used to treat a broad spectrum of cancers including head and neck, ovarian, cervical, stomach, bladder, sarcoma, lymphoma, testicular cancer and others.

The objective of this study is to design and synthesize rhodamine derivatives that can be used for the construction of geometrically …

The Impact Of Peptide Nucleic Acid Fluorescence In Situ Hybridization (Pna Fish®) Rapid Diagnostic Testing On The Initiation Of Appropriate Antifungal Therapy In Patients With Candida Species Bloodstream Infections, Jenna Lee Ksiazkiewicz

Undergraduate Honors Thesis Collection

Background: Traditional methods for detecting positive blood cultures include the use of broth bottles with sensitive indicators for growth. These techniques can take 24-48 hours to signal a positive test. Another 24 hours are often required to determine the species of the organism. The use of rapid diagnostic testing for Candida species bloodstream infections provides accurate species identification in less than two hours.

Objective: Evaluate the time to appropriate antifungal therapy in patients in which rapid diagnostic testing was utilized.

Methods: This study was a retrospective, observational cohort of patients who had positive blood cultures for Candida species and had …

Periodontal Disease: Molecular Visualization Through Computer Modeling And 3d Printing, Catherine Chatowsky

Senior Honors Projects

Periodontal disease is a common infection that damages gingival tissue and creates jawbone destruction that can lead to the loosening or loss of teeth. Hundreds of diverse bacterial species reside in the harsh environment of the oral cavity. The creation of plaque and biofilms serve to allow the bacteria to avoid immune-mediated destruction. This project analyzed periodontal disease pathogens using molecular printing 3D visualization. Two bacterial species (T. denticola and P. gingivalis) were chosen from the public resource: Research Collaboratory for Structural Bioinformatics: Protein Data Bank. T. denticola was a bacteria found to have a binding protein (FhbB) …

Functional Activity And Switching Of Novel Cannabinergic Ligands, Bret Alan Koertge

Theses and Dissertations (ETD)

Pursuant to the discovery of the cannabinoid receptors, research in this field has grown exponentially over the last 2 decades. With their utility in various disease states such as heart disease, cancer, stroke, neurodegenerative and inflammation, cannabinoids stand poised to become a great therapeutic agent. This research seeks to better understand the functional mechanism of cannabinoids, in the hopes of ascertaining which molecular attributes confer desirable selectivity and functional activity.

Looking first at classical benzchromene core analogues, we have shown that presence of an aromatic substitution at C-1' imparts a CB1 agonist, CB2 antagonist. This is a unique mechanism and …

Evaluating The Non-Evidence Based Practice Of Rounding Serum Creatinine In The Elderly And The Impact On Medication Dosing, Kelly Lynn Roden

Undergraduate Honors Thesis Collection

Background: The Cockcroft and Gault equation is widely accepted in practice as the most appropriate way to calculate an estimated creatinine clearance. Geriatric patients often present with reduced muscle mass, and therefore lower creatinine production, due to normal changes in body composition associated with aging. Because serum creatinine and creatinine clearance are inversely proportional using the Cockcroft and Gault equation, a lower serum creatinine may falsely overestimate renal function in the elderly population. Rounding to a normal serum creatinine is believed by some practitioners to prevent over estimation of creatinine clearance and renal function.

Objective: The objective of this study …

Pneumonia: Not Getting Vaccinated May Take Your Breath Away, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

A Simple Method For Discovering Druggable, Specific Glycosaminoglycan-Protein Systems. Elucidation Of Key Principles From Heparin/Heparan Sulfate-Binding Proteins, Aurijit Sarkar, Umesh R. Desai

Psychology Publications

Glycosaminoglycans (GAGs) affect human physiology and pathology by modulating more than 500 proteins. GAG-protein interactions are generally assumed to be ionic and nonspecific, but specific interactions do exist. Here, we present a simple method to identify the GAG-binding site (GBS) on proteins that in turn helps predict high specific GAG–protein systems. Contrary to contemporary thinking, we found that the electrostatic potential at basic arginine and lysine residues neither identifies the GBS consistently, nor its specificity. GBSs are better identified by considering the potential at neutral hydrogen bond donors such as asparagine or glutamine sidechains. Our studies also reveal that an …

Acid-Suppressing Agents And Risk For Clostridium Difficile Infection In Pediatric Patients, Katelyn E. Brown, Chad A. Knoderer, Kristen R. Nichols, Ashley S. Crumby

Scholarship and Professional Work – COPHS

Background. Acid-suppressing agents have been associated with increased Clostridium difficile infection (CDI) in adults. The objective of this study was to evaluate the association of acid-suppressing therapy with the development of CDI in the pediatric population.

Methods. This was a retrospective case-control study. Children aged 1 through 17 years with a positive C difficile polymerase chain reaction (PCR) result obtained between June 1, 2008, and June 1, 2012, were randomly matched to a control population selected from patients with negative PCR.

Results. A total of 458 children were included. No difference was observed in acid-suppressive therapy prior …

Implementing Extended-Infusion Cefepime As Standard Of Care In A Children’S Hospital: A Prospective Descriptive Study, Kristen R. Nichols, Lauren C. Karmire, Elaine G. Cox, Michael B. Kays, Chad A. Knoderer

Scholarship and Professional Work – COPHS

Background: Extended-infusion cefepime (EIC) has been associated with decreased mortality in adults, but to our knowledge, there are no studies in children.

Objective: The objective of this study was to determine the feasibility of implementing EIC as the standard dosing strategy in a pediatric population.

Methods: This was a descriptive study of children aged 1 month to 17 years, including patients in the intensive care unit, who received cefepime after admission to a freestanding, tertiary care children’s hospital. Patients were excluded if they were admitted to the neonatal intensive care unit or received cefepime in the outpatient, …

Self-Assembling Modified Β -Cyclodextrin Conjugated Sirna Nanoparticles And Liposomal Sirna Efficiently Knock Down The Mutant Huntingtin Gene In A Modified Pc-12 Cell Line, Rukmini Ladi, Sudip Das, Nandita Das

Scholarship and Professional Work – COPHS

Purpose: To formulate and characterize liposomal siRNA (LP-siRNA) and cationic β-cyclodextrin siRNA (CD-siRNA) nanoparticle complexes and evaluate their efficacy in knockdown of mutant Huntingtin protein (mHtt) in a modified PC-12 cell line.

Curcuminoid In Nanoemulsion Formulations Cause Enhanced Cell Death In The Hela Cancer Cell Culture Model, Nikita Kheradia, Nandita Das, Sudip Das

Scholarship and Professional Work – COPHS

Purpose: To formulate and characterize curcuminoid (insoluble chemoprevention agent) loaded nanoemulsions and evaluate their cytotoxicity in HeLa cells.

Stribild: A Review Of Component Characteristics And Combination Drug Efficacy, Derek E. Murrell, Jonathan P. Moorman, Sam Harirforoosh

Pharmacy Faculty Articles and Research

BACKGROUND: Numerous methods have been devised to combat human immunodeficiency virus (HIV) replication and disease progression. Composed of an integrase strand transfer inhibitor, a pharmacoenhancer, and two reverse transcriptase inhibitors, Stribild is a relatively new combination HIV drug formulated for once-a-day dosing.

METHODS: Relevant information, original research articles and reviews, were gathered primarily through the use of the PubMed database. The search was conducted without date restrictions in order to collect both historical and recent information concerning HIV, individual drugs, and combinations for a thorough overview.

RESULTS: Stribild, when taken with food, provides therapeutic drug concentrations as …

Formulation And In Vitro Evaluation Of Niacin-Loaded Nanoparticles To Reduce Prostaglandin Mediated Vasodilatory Flushing, Dustin L. Cooper, Jennifer A. Carmical, Peter C. Panus, Sam Harirforoosh

Pharmacy Faculty Articles and Research

OBJECTIVE: Niacin, activating G-protein coupled receptor (GPR) 109A, stimulates release of vasodilatory prostaglandins (PGs) such as PGE2 which can elicit niacin-associated flushing side effects. Poly-lactic-co-glycolic acid (PLGA) and poly-lactic acid (PLA) are used in nanoparticle (NP) drug delivery to reduce adverse effects and modulate drug release. Our study evaluated the in vitro effects of niacin-loaded PLGA or PLA-NPs on PGE2 expression in whole human blood as a model for niacin-induced flushing.

MATERIALS AND METHODS: NPs were formulated using a solvent evaporation process and characterized by size, polydispersity, zeta potential, drug entrapment, morphology, and drug release. NP in vitro …

Elaboration And Design Of Α7 Nachr Negative Allosteric Modulators, Osama I. Alwassil

Theses and Dissertations

α7 Neuronal nicotinic acetylcholine receptors are one of two major classes of receptors responsible for cholinergic neurotransmission in the central nervous system. The existence of α7 neuronal nAChRs in different regions of the nervous system suggests their involvement in certain essential physiological functions as well as in disorders such as Alzheimer’s disease (AD), drug dependence, and depression. This project was aimed toward the discovery and development of small–molecule arylguanidines that modulate α7 nAChR function with improved subtype-selectivity through an allosteric approach. Identifying the required structural features of these small molecules allowed optimization of their negative allosteric modulator (NAM) actions at …

Metal Organic Frameworks (Mofs) And Porous Organic Polymers (Pops) For Heterogeneous Asymmetric Catalysis, Youngran Ji

USF Tampa Graduate Theses and Dissertations

The administration of enantiopure drugs brings advantages such as improved efficacy, more predictable pharmacokinetics and reduced toxicity from the point of view of the pharmaceutical area.[1] For this reason, a tremendous amount of supply and demand for enantiomeric pure compounds has been shown not only in market, but industry and academia.[^2-4] According to the industry publication Genetic Engineering and Biotechnology News (GEN) in 2014, 22 billion dollars were accounted for enantiopure form of drugs such as Sovaldi® (Sofosbuvir), Crestor® (Rosuvastatin), and Advair® (fluticasone/salmeterol).

The fact that one enantiomer can be pharmacologically effective whereas the other enantiomer can be …

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …