Pharmacy and Pharmaceutical Sciences Commons^™

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Synthesis And Biological Evaluation Of Novel Resveratrol And Combretastatin A4 Derivatives As Potent Anti-Cancer Agents, Nikhil Reddy Madadi

Theses and Dissertations--Pharmacy

Resveratrol has been reported as a potential anticancer agent but cannot be used as an antitumor drug due to its chemical and metabolic instability. We have designed and synthesized 184 novel compounds related to resveratrol in an attempt to produce more potent and drug-like molecules. We have identified a tetrazole analog of resveratrol, ST-145(a) as a lead anticancer agent from the resveratrol analog series of compounds with a GI₅₀ value of less than 10nM against almost all the human cancer cell lines in the National Cancer Institute’s screening panel.

In a separate study, we tested the hypothesis that the …

Multi-Component Microparticulate/Nanoparticulate Dry Powder Inhalation Aerosols For Targeted Pulmonary Delivery, Xiaojian Li

Theses and Dissertations--Pharmacy

The aim of the work was to design, manufacture, and characterize targeted multi-component dry powder aerosols of (non-destructive) mucolytic agent (mannitol), antimicrobial drug (tobramycin or azithromycin), and lung surfactant mimic phospholipids (DPPC:DPPG=4:1 in molar ratio). The targeted dry powder for inhalation formulation for deep lung delivery with a built-in rationale of specifically interfering several disease factors of chronic infection diseases in deep lungs such as cystic fibrosis, pneumonia, chronic bronchitis, and etc. The dry powder aerosols consisting of selected chemical agents in one single formulation was generated by using spray drying from organic solution.

The physicochemical properties of multi-component dry …

Human Butyrylcholinesterase Mutants For Cocaine Detoxification, Shurong Hou

Theses and Dissertations--Pharmacy

Cocaine is one of the most reinforcing drugs of abuse and has caused serious medical and social problems. There is no FDA-approved medication specific for cocaine. It is of a high priority to develop an effective therapeutic treatment for cocaine abuse. Human butyrylcholinesterase (BChE) has been recognized as a promising candidate of enzyme therapy to metabolize cocaine into biologically inactive metabolites and prevent it from reaching central nervous system (CNS). However, the catalytic activity of wide-type human BChE against cocaine is not sufficiently high for treatment of cocaine abuse. Dr. Zhan’s lab has successfully designed and discovered a series of …

Lobelane Analogs With Various Methylene Linker Lengths And Acyclic Lobelane Analogs As Potential Pharmacotherapies To Treat Methamphetamine Abuse, Zheng Cao

Theses and Dissertations--Pharmacy

Methamphetamine interacts with vesicular monoamine transporter-2 (VMAT2) to inhibit dopamine (DA) uptake and promotes DA release from presynaptic vesicles, increasing cytosolic DA available for methamphetamine-induced reverse transport by DA transporters. By inhibiting VMAT2, lobelane, a defunctionalized, saturated lobeline analog, decreases methamphetamine-evoked DA release and methamphetamine self-administration in rats. In this dissertation structure-activity relationships around the lobelane structure were investigated on racemic lobelane analogs with varying methylene linker lengths at central piperidine ring. Affinity for dihydrotetrabenazine (DTBZ) sites on VMAT2 and for inhibition of VMAT2 function was determined to be 0.88-63 and 0.024-4.6 µM, respectively, and positively correlated. The most potent …

Investigating Structure And Protein-Protein Interactions Of Key Post-Type Ii Pks Tailoring Enzymes, Theresa E. Downey

Theses and Dissertations--Pharmacy

Type II polyketide synthase (PKS) produced natural products have proven to be an excellent source of pharmacologically relevant molecules due to their rich biological activities and chemical scaffolds. Type II-PKS manufactured polyketides share similar polycyclic aromatic backbones leaving their diversity to stem from various chemical additions and alterations facilitated by post-PKS tailoring enzymes. Evidence suggests that post-PKS tailoring enzymes form complexes in order to facilitate the highly orchestrated process of biosynthesis. Thus, protein-protein interactions between these enzymes must play crucial roles in their structures and functions. Despite the importance of these interactions little has been done to study them. In …

Flavonoids With Novel Nicotinic Activity As Potential Pharmacotherapies To Treat Ethanol-Induced Neurotoxicity, Joseph A. Lutz

Theses and Dissertations--Pharmacy

Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as excitotoxicity during ethanol withdrawal. The primary therapeutic implication is that ethanol-induced neurotoxicity requires multifunctional pharmacotherapies which reduce all mechanisms. Using an innovative pharmacological high throughput screening method on a large plant extract library we discovered flavonoids with alpha7 nicotinic acetylcholine receptor (nAChR) activity. In addition to their well-known anti-inflammatory and antioxidant properties, this novel activity means they can potentially reduce excitotoxicity and therefore makes them ideal for inhibition of ethanol-induced neurotoxicity. Rhamnetin, the candidate compound, …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

Programmable Folding Of Fusion Rna In Vivo And In Vitro Driven By Prna 3wj Motif Of Phi29 Dna Packaging Motor, Dan Shu, Emil F. Khisamutdinov, Le Zhang, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

Misfolding and associated loss of function are common problems in constructing fusion RNA complexes due to changes in energy landscape and the nearest-neighbor principle. Here we report the incorporation and application of the pRNA-3WJ motif of the phi29 DNA packaging motor into fusion RNA with controllable and predictable folding. The motif included three discontinuous ∼18 nucleotide (nt) fragments, displayed a distinct low folding energy (Shu D et al., Nature Nanotechnology, 2011, 6:658–667), and folded spontaneously into a leading core that enabled the correct folding of other functionalities fused to the RNA complex. Three individual fragments dispersed at any …

Knowledge And Provision Practices Of Misoprostol Among Pharmacies In Senegal, Ramatoulaye Ndao, Babacar Mane, Eva Burke, Nafissatou Diop, Kate Reiss, Thoai Ngo, Katharine Footman, Maaike Van Min

Reproductive Health

In developing countries, postpartum hemorrhage and complications related to unsafe abortions are direct causes of maternal death. In Senegal, actions have been undertaken by the government to reduce this burden and significant advances have been made in these areas in recent years. However, progress is still necessary to achieve the Millennium Development Goals for the reduction of the maternal mortality rate to the target numbers by 2015. The objective of the study was to understand the knowledge about, availability of, and practices in the provision of misoprostol at pharmacies in Dakar, Senegal, to ensure correct delivery of the product. Pharmacists …

Dereplication And Prioritization Of Natural Product Extracts For Antifungal Drug Discovery, Kara Fowler

Honors Theses

The prevalence of opportunistic fungal infections in hospital settings are at alarming rates. Through technological advances in natural product research, plants have become a useful source for antifungal drug discovery. More samples can be screened at once, fractionated in less time, and biologically tested at smaller quantities. However, isolating antifungal compounds from these plant extracts and determining their specific chemical makeup can still take up a significant amount of time. Therefore, this thesis presents a prioritization technique to prevent the need to isolate every compound within an active fraction. With the guidance of literature research on the genus and species …

Mississippi Pharmacists' Knowledge And Attitudes About Pharmacy Compounding Safety And Regulation, Kimberly Allen

Honors Theses

Introduction: Pharmacy compounding, which is defined by The Food and Drug Administration (FDA) as a practice in which a licensed pharmacist combines, mixes, or alters ingredients in response to a prescription to create a medication tailored to the medical needs of an individual patient,1 has gained recent attention at both national and state levels. Outbreaks of adverse events associated with pharmacy compounding have led to many proposed and enacted changes in how to appropriately and best regulate traditional compounding pharmacies and those that act as manufacturers. Given such recent controversies and potential confusion as to exactly how compounding is regulated, …

Reproductive And Multigenerational Effects Of Dietary Benzo[A]Pyrene Exposure In Zebrafish, Mallory White

Honors Theses

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is a known carcinogen that also acts as an endocrine disruptor. Multigenerational impacts of PAH exposure are suggested in human cohort studies. To investigate mechanisms and developmental phenotypes associated with a dietary BaP exposure, zebrafish (Danio rerio) were used. We hypothesized that BaP exposure would cause: 1) phenotypic malformations in the gonad that would affect reproductive success; 2) developmental deformities in the offspring that would lead to decreased survival and ability to reproduce without additional BaP exposure; and 3) changes in gene expression that would be conserved across generations and related …

Bullying In The Clinical Training Of Pharmacy Students, Katherine K. Knapp, Patricia A. Shane, Debra Sasaki-Hill, Keith Yoshizuka, Paul Chan, Thuy Vo

Faculty Publications & Research of the TUC College of Pharmacy

Objective. To determine whether bullying is a significant factor in the clinical training of pharmacy students.

Methods. The literature as well as the Accreditation Council for Pharmacy Education (ACPE) Standards and American Association of Colleges of Pharmacy (AACP) surveys were reviewed for mention and/or measurement of bullying behaviors in the clinical training of pharmacy students. The authors used a Delphi process to define bullying behavior. The consensus definition was used to analyze 2,087 in-house student evaluations of preceptors for evidence of bullying behaviors. The authors mapped strings of text from in-house student comments to different, established categories of …

Pharmacy Students’ Performance And Perceptions In A Flipped Teaching Pilot On Cardiac Arrhythmias, Terri H. Wong, Eric J. Ip, Ingrid C. Lopes, Vanishree Rajagopalan

Faculty Publications & Research of the TUC College of Pharmacy

Objective. To implement the flipped teaching method in a 3-class pilot on cardiac arrhythmias and to assess the impact of the intervention on academic performance and student perceptions.

Design. An intervention group of 101 first-year pharmacy students, who took the class with the flipped teaching method, were supplied with prerecorded lectures prior to their 3 classes (1 class in each of the following subjects: basic sciences, pharmacology, and therapeutics) on cardiac arrhythmias. Class time was focused on active-learning and case-based exercises. Students then took a final examination that included questions on cardiac arrhythmias. The examination scores of the …

Cardiolipin Prevents Membrane Translocation And Permeabilization By Daptomycin, Tianhua Zhang, Jawad K. Muraih, Nasim Tishbi, Jennifer Herskowitz, Rachel L. Victor, Jared Silverman, Stephanie Uwumarenogie, Scott D. Taylor, Michael Palmer, Evan Mintzer

Lander College of Arts and Sciences Publications and Research

Daptomycin is an acidic lipopeptide antibiotic that, in the presence of calcium, forms oligomeric pores on membranes containing phosphatidylglycerol. It is clinically used against various Gram-positive bacteria such as Staphylococcus aureus and Enterococcusspecies. Genetic studies have indicated that an increased content of cardiolipin in the bacterial membrane may contribute to bacterial resistance against the drug. Here, we used a liposome model to demonstrate that cardiolipin directly inhibits membrane permeabilization by daptomycin. When cardiolipin is added at molar fractions of 10 or 20% to membranes containing phosphatidylglycerol, daptomycin no longer forms pores or translocates to the inner membrane leaflet. Under …

Pharmacists' Preparedness For Acute Medical Emergencies, James W. Parrett

Electronic Theses and Dissertations

Purpose/Objectives: This project studied how prepared community pharmacists are to respond to acute medical emergencies, as well as their perceived efficacy in addressing these situations. Specifically, it considered what training pharmacists have for responding to medical emergencies, what emergency medical equipment pharmacies have on-hand, the frequency that medical emergencies occur within pharmacies, and the types of emergencies encountered. It also measured self and collective efficacy of pharmacists in responding to medical emergencies within their pharmacy to determine if differences in self-efficacy or collective efficacy exist. Methods: This study utilized a cross-sectional, non-experimental, descriptive design via a self-administered, Internet-based survey distributed …

Management Of Breast Cancer In The Medicaid Population, Rohan Mahabaleshwarkar

Electronic Theses and Dissertations

Breast cancer is the second most comcancer and the second leading cause of cancer-related death among women. The current project examined some key issues important for effective breast cancer management in the Medicaid population. Medicaid is one the largest healthcare insurance systems in the US providing coverage to more than 60 million low-income individuals. As a part of this project, three studies were conducted. The first study determined the healthcare burden associated with breast cancer in the form of healthcare use (inpatient, outpatient, and emergency room [ER] visits) and costs associated with the condition in the Medicaid population. Significant healthcare …

Cranberry Metabolites With Urinary Anti-Adhesion Activity, Christina M. Coleman

Electronic Theses and Dissertations

The fruit of the American cranberry (Vaccinium macrocarpon Aiton, Ericaceae) is a comfood and a top selling dietary supplement in the U.S. Cranberry juice is traditionally used for the prevention of urinary tract infections (UTIs), many of which are caused by P-fimbriated Escherichia coli. Human urine produced after cranberry juice consumption can prevent E. coli adhesion, but the urinary metabolites responsible for this activity are currently not known. High-molecular weight components of cranberry juice, specifically proanthocyanidin oligomers (PACs), are currently believed to be responsible for the ability of cranberry juice to prevent UTIs. Cranberry PACs can prevent the adherence of …

Structure, Synthesis And Biological Activity Of Harmful Algal Bloom Toxins From Karlodinium Sp. And Exploration Of Microbial Derived Natural Products, Amanda Leigh Waters

Electronic Theses and Dissertations

This work features natural products isolated from both the marine and microbial environments. Part I focuses on the elucidation of toxins from harmful algal blooms (HAB). The HAB dinoflagellate Karlodinium veneficum produces a harmful suite of molecules identified as the karlotoxins (KmTx) that have been implicated in massive fish kills pan-globally. Nine new karlotoxin congeners were isolated from various Karlodinium blooms around the world and utilizing the structure of KmTx2 were characterized using overlaid 2D NMR techniques. Due to the contrasting conformational differences between KmTx and the closely related amphidinols, the absolute configuration of KmTx was further evaluated by extensive …