Pharmacy and Pharmaceutical Sciences Commons^™

Development Of Hif-1Α/Hif-1Β Heterodimerization Inhibitors Using A Novel Bioluminescence Reporter Assay System For In Vitro High Throughput Screening And In Vivo Imaging, Yun-Chen Chiang

Dissertations & Theses (Open Access)

Tumor growth often outpaces its vascularization, leading to development of a hypoxic tumor microenvironment. In response, an intracellular hypoxia survival pathway is initiated by heterodimerization of hypoxia-inducible factor (HIF)-1α and HIF-1β, which subsequently upregulates the expression of several hypoxia-inducible genes, promotes cell survival and stimulates angiogenesis in the oxygen-deprived environment. Hypoxic tumor regions are often associated with resistance to various classes of radio- or chemotherapeutic agents. Therefore, development of HIF-1α/β heterodimerization inhibitors may provide a novel approach to anti-cancer therapy. To this end, a novel approach for imaging HIF-1α/β heterodimerization in vitro and in vivo was developed in this study …

Hydrodynamic Effects Of A Cannula In A Usp Dissolution Testing Apparatus 2, Qianqian Liu

Theses

Dissolution testing is routinely used in the pharmaceutical industry to provide in vitro drug release information for drug development and quality control purposes. The USP Testing Apparatus 2 is the most common dissolution testing system for solid dosage forms. Usually, sampling cannulas are used to take samples manually from the dissolution medium. However, the inserted cannula can alter the normal fluid flow within the vessel and produce different dissolution testing results.

The hydrodynamic effects introduced by a permanently inserted cannula in a USP Dissolution Testing Apparatus 2 were evaluated by two approaches. Firstly, the dissolution tests were conducted with two …

Effect Of Tablet Compression On The Dissolution Of Aspirin Tablets Using A Novel Off-Center Paddle Impeller (Opi) Dissolution Testing System, Chuan Sun

Theses

In the pharmaceutical industry, dissolution testing is routinely carried out to determine the dissolution rate of oral solid dosage forms. Among several testing devices, the USP Dissolution Apparatus 2 is the device most commonly used. However, despite its widespread use, this apparatus has been shown to produce test failures and to be very sensitive to a number of small geometry changes.

The objective of this study was to determine whether a novel dissolution system termed “OPI” for “off-center paddle impeller” was sensitive enough to determine differences in tablet dissolution profiles caused by different compression pressure during the tablet manufacturing process. …

Hollow Fiber Membrane-Based Air Gap Membrane Distillation, Xuan Wang

Theses

Membrane Distillation (MD) is a thermally-driven separation process. In this research, desalination of 1 % NaCl solution is achieved by one type of MD namely, Air Gap Membrane Distillation (AGMD). The characteristics of AGMD are evaluated by using a hollow-fiber-set-based compact device. Hot brine solution and cold water are passed through two different fiber sets separately: porous hydrophobic polyvinylidene fluoride hollow fibers of the E type (PVDF E) and solid polypropylene (PP) hollow fibers. Vapor from the hot brine crosses the membrane pores of the PVDF fibers and the air gap, and finally condenses over the surface of solid hollow …

Dissolution Of Different Commercial Aspirin Tablets Using A Novel Off-Center Paddle Impeller (Opi) Dissolution Testing System, Yang Qu

Theses

Dissolution testing is routinely conducted in the pharmaceutical industry to provide in vitro drug release information for quality control purposes. The most common dissolution testing system for solid dosage forms is the United States Pharmacopeia (USP) Dissolution Testing Apparatus 2. In this work, a modified Apparatus 2, termed "OPI" System for "off-center paddle impeller," in which the impeller is placed 8 mm off center in the vessel is tested to determine its sensitivity to differentiate between the dissolution profiles of differently formulated and manufactured tablets. Dissolution tests are conducted with both the OPI System and the Standard System using three …

Qsar Modeling Of Chemical Penetration Enhancers Using Novel Replacement Algorithms, Hui Qiu

Theses

The applications of transdermal delivery are limited because of the resistance of the skin to drug diffusion. Only potent drugs, with molecular weight less than 500 Da, are suitable to cross the skin barrier. Chemical Penetration Enhancers (CPEs) are used to promote the absorption of solutes across the dermal layers. In this investigation, a Quantitative Structure-Activity Relationship (QSAR) model is applied to relate chemical penetration enhancer structures with the flux enhancement ratio through a statistical approach.

A database, consisting of 61 non-polar CPEs, is selected for the study. Each compound is represented by 777 QSAR descriptors, which encode the physical …

Engineering Spores To Display G Protein-Coupled Receptors For Directed Evolution, Alyssa Misoo Kim

Theses

All human cells are surrounded by a plasma membrane made from a phospholipid bilayer, which is responsible for maintaining a biologically active species, while stopping entry of deleterious substances from the outside. G protein-coupled receptors (GPCRs) are the membrane proteins, which transmit signals across the cell membrane. GPCRs are involved in almost every physiological process, and irregular control leads to pathological conditions. Therefore, they are major drug targets. Crystal structure determination is required to understand the molecular details of activation/deactivation. However, GPCRs are difficult to crystallize because of stability issues. An efficient protein engineering system needs to be developed. The …

A Series Of Pharmaceutical Technology Concepts Applied To Pediatric Formulations, Hao Lou

Theses and Dissertations (ETD)

Pediatric formulations have received great attention from regulatory agencies in the United States and Europe. Since solid dosage forms such as tablets and capsules will not be able to improve pediatric patients’ compliance, customized pediatric formulations are needed. In response, formulators in the pharmaceutical industry have made significant effort into developing various pediatric formulations. However, developing satisfactory pediatric formulations is a process that is guided by case by case basis. The objective of this current study was to apply the scientific pharmaceutical technology concepts into developing modern pediatric formulations. We have shown that the drug delivery design will be affected …

Low Soluble Drug Encapsulation Based On Architecture Of Layer-By-Layer Assembly For Longer Circulation Time And Targeted Therapy, Pravin Pattekari

Doctoral Dissertations

A combined effect of sonication and layer-by-layer assembly (LbL) enhances the solubility of many poorly soluble inorganic and organic materials by forming stable particles with ca. 200 nm size and up to 90 wt% of loading. The entire method is reproducible, easy-to-handle, and flexible for varying surface properties according to the application of the materials. The method develops good colloidal stability of materials in buffers and maintains architecture for future improvement. A top-down approach, with a combined effect of sonication and LbL assembly, ruptures the material and allows adsorption of oppositely charged polyelectrolytes simultaneously. Thus, the approach is applicable for …

Novel Therapy For Nicotine Addiction In Alcohol Dependent Rats, Bethany Ann Stennett

UNF Graduate Theses and Dissertations

The co-dependence of nicotine and alcohol addiction occurs at high rates, complicates treatment, and is often associated with significant morbidity and mortality. Treatment options of alcohol and tobacco co-dependence are limited. Currently, there are drugs available for nicotine dependence or alcohol dependence. However, there are no therapeutic drugs available on the market for the co-dependence of nicotine and alcohol. Therefore, and important opportunity of new therapeutic options and drug development has presented itself. NT69L, a non-selective neurotensin (NT) agonist, provides a potential novel therapy for nicotine addiction in alcoholics by interacting with the common neurotransmitter circuits supporting the rewarding process …

Towards Elucidation Of A Viral Dna Packaging Motor, Chad T. Schwartz

Theses and Dissertations--Pharmacy

Previously, gp16, the ATPase protein of phi29 DNA packaging motor, was an enigma due to its tendency to form multiple oligomeric states. Recently we employed new methodologies to decipher both its stoichiometry and also the mechanism in which the protein functions to hydrolyze ATP and provide the driving force for DNA packaging. The oligomeric states were determined by biochemical and biophysical approaches. Contrary to many reported intriguing models of viral DNA packaging, it was found that phi29 DNA packaging motor permits the translocation of DNA unidirectionally and driven cooperatively by three rings of defined shape. The mechanism for the generation …

The Pharmacokinetics Of Metal-Based Engineered Nanomaterials, Focusing On The Blood-Brain Barrier, Mo Dan

Theses and Dissertations--Pharmacy

Metal-based engineered nanomaterials (ENMs) have potential to revolutionize diagnosis, drug delivery and manufactured products, leading to greater human ENM exposure. It is crucial to understand ENM pharmacokinetics and their association with biological barriers such as the blood-brain barrier (BBB). Physicochemical parameters such as size and surface modification of ENMs play an important role in ENM fate, including their brain association. Multifunctional ENMs showed advantages across the highly regulated BBB. There are limited reports on ENM distribution among the blood in the brain vasculature, the BBB, and brain parenchyma.

In this study, ceria ENM was used to study the effect of …

Formulation Optimization For Pore Lifetime Enhancement And Sustained Drug Delivery Across Microneedle Treated Skin, Priyanka Ghosh

Theses and Dissertations--Pharmacy

Microneedle (MN) enhanced drug delivery is a safe, effective and efficient enhancement method for delivery of drug molecules across the skin. The “poke (press) and patch” approach employs solid stainless steel MN to permeablize the skin prior to application of a regular drug patch over the treated area. It has been previously shown that MN can be used to deliver naltrexone (NTX) at a rate that provides plasma concentrations in the lower end of the therapeutic range in humans. The drug delivery potential of this technique is, however, limited by the re-sealing of the micropores in a 48-72h timeframe. The …

Computational Modeling, Design, And Characterization Of Cocaine-Metabolizing Enzymes For Anti-Cocaine Medication, Lei Fang

Theses and Dissertations--Pharmacy

Cocaine is a widely abused and addictive drug, resulting in serious medical and social problems in modern society. Currently, there is no FDA-approved medication specific for cocaine abuse treatment. The disastrous medical and social consequences of cocaine abuse have made the development of an anti-cocaine medication a high priority. However, despite decades of efforts, traditional pharmacodynamic approach has failed to yield a truly useful small-molecule drug due to the difficulties inherent in blocking a blocker like cocaine without affecting the normal functions of the transporters or receptors. An alternative approach, i.e. pharmacokinetic approach, is to interfere with the delivery of …

High-Activity Mutants Of Human Butyrylcholinesterase For Cocaine Abuse Treatment, Liu Xue

Theses and Dissertations--Pharmacy

Cocaine is a widely abused drug without an FDA-approved medication. It has been recognized as an ideal anti-cocaine medication to accelerate cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e. butyrylcholinesterase (BChE)-catalyzed hydrolysis. However, the native BChE has a low catalytic activity against cocaine. We recently designed and discovered a set of BChE mutants with a high catalytic activity specifically for cocaine. An ideal, therapeutically valuable mutant of human BChE should have not only a significantly improved catalytic activity against cocaine, but also certain selectivity for cocaine over neurotransmitter acetylcholine (ACh) such …