Medicine and Health Sciences Commons^™

Topical Formulation For Stimulating Sweat Secretion As An Alternative To Iontophoresis, Tasnim Fatima

Electronic Theses and Dissertations

Sweat test or pilocarpine iontophoresis test is the existing method for diagnosis of cystic fibrosis that is recommended to perform at 48 hours after birth. However, the current method is painful, with several side effects such as full thickness skin burn, skin rash, erythema etc. Therefore, the purpose of this study is to develop a pilocarpine topical formulation which can stimulate sweat secretion when applied on skin without iontophoresis. Several formulations with Transcutol®, polyethylene glycol 400 (PEG 400), Polyethylene glycol 200 (PEG 200), menthol and salicylic acid (SA) each at varying concentrations were screened as penetration enhancers. In vitro penetration …

Jorunnamycin A Induces Anoikis In Human Lung Cancer H460 Cells, Gea Abigail Uy Ecoy

Chulalongkorn University Theses and Dissertations (Chula ETD)

Metastasis is a key driving force behind the high mortality rate associated with lung cancer. Anoikis is a type of apoptosis triggered by the loss of appropriate cell attachment and its loss via several cancer cell survival strategies has been shown to promote transformation and metastasis. Jorunnamycin A, a promising renieramycin-type anti-cancer compound, is a bistetrahydroisoquinolinequinone alkaloid that has been recently isolated from the Thai blue sponge Xestospongia sp. for use in this study. Herein, we report the anti-metastasis activity of jorunnamycin A, a bistetrahydroisoquinolinequinone isolated from the Thai blue sponge Xestospongia sp. evidenced by its suppression of epithelial-to-mesenchymal-transition, sensitization …

Efforts To Reduce Concomitant Opioid And Benzodiazepine Prescribing At The Lexington Veterans Affairs Medical Center, Kaitlyn A. Staton

MPA/MPP/MPFM Capstone Projects

The United States is in the throes of an opioid epidemic. Any person who uses an opioid medication may experience an intentional or unintentional overdose. An overdose is more likely to occur when an individual ingests an opioid in combination with certain classes of medications, such as benzodiazepines or nonbenzodiazepines (Z-drugs). These medications are more likely to cause sedation and respiratory depression when taken together. Veterans, due to their unique mental and physical health challenges, are more likely to experience an overdose when they receive a combination of opioid therapy with benzodiazepine or Z-drug therapy as opposed to a single …

Regulatory Issues Concerning The Preclinical Testing Of Synthetic Peptides, Vamsi Vardhan Niraghatam

Master's Theses and Doctoral Dissertations

Any new drug or biological product undergoes rigorous testing in animals and humans for review by the United States Food and Drug Administration (FDA) before it becomes available for human use. A sponsor files an investigational new drug (IND) application with the FDA with supporting animal data, after which testing is continued with humans. There is sufficient guidance from the FDA on new small molecules and biological products as to which preclinical studies are to be conducted. Synthetic peptides present a unique scenario in which a case-by-case approach is needed for the conduct of preclinical studies. For peptides containing components …

Current Approaches And New Developments In The Pharmacological Management Of Tourette Syndrome., Julio Quezada, Keith A. Coffman

Manuscripts, Articles, Book Chapters and Other Papers

Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology characterized by spontaneous, involuntary movements and vocalizations called tics. Once thought to be rare, TS affects 0.3-1% of the population. Tics can cause physical discomfort, emotional distress, social difficulties, and can interfere with education and desired activities. The pharmacologic treatment of TS is particularly challenging, as currently the genetics, neurophysiology, and neuropathology of this disorder are still largely unknown. However, clinical experience gained from treating TS has helped us better understand its pathogenesis and, as a result, derive treatment options. The strongest data exist for the antipsychotic agents, both typical …

Predictors Of Dental Opioid Analgesic Prescribing, Opioid Use And Dental Emergency Department Visits In The Mississippi Medicaid Population, Chukwuebuka Dibie

Electronic Theses and Dissertations

OBJECTIVES: The objectives of this study were: (1) to determine prevalence of opioid analgesics prescribing for non-ED dental related visits in the Mississippi Medicaid population, (2) to assess predictors of receiving opioid analgesics following non-ED dental related events among Mississippi Medicaid beneficiaries, and (3) to determine prevalence of opioid analgesic prescribing for dental related emergency departments (ED) visits in the Mississippi Medicaid population. METHODS: A retrospective, cross-sectional, observational database analysis using Mississippi Medicaid administrative claims data from January 1, 2015 to December 31, 2016. Beneficiaries with dental related visits were included in this study. Descriptive statistics were utilized to assess …

Fluorinated Organic Molecules For Medicinal Applications, Munia Sowaileh

Electronic Theses and Dissertations

The significant applications of fluorinated molecules in the pharmaceutical, agrochemical, and material sciences make them attractive synthetic targets. Difluoromethylation methods are of exceptional value and a limited number of techniques are available to perform that transformation. The primary method for introducing CF2 groups is through the use of difluoroenolates. Difluoroenolates can be generated from α-keto pentafluoro gem -diols under mild conditions. The process involves the cleavage of carbon-carbon bond and the release of trifluoroacetate. The release of trifluoroacetate is a versatile method to generate fluorinated molecules. We explored the utility of this method in generating various fluorinated moieties including α,α-difluoroketones, …

Novel Application Of Twin Screw Extruder On Production Of Diverse Formulations, Xingyou Ye

Electronic Theses and Dissertations

Twin-screw extruder has attracted considerable attention in the pharmaceutical industry as an alternative processing instrument due to its advantages compared to other conventional equipment, such as economical processing, small footprint, reduced in-process times, solvent-free and continuous processing. These superiorities have led to the application of twin-screw extruder to produce numerous dosage forms, including pellets, tablets and films. Many other formulations production can also be beneficial from the introduction of twin-screw extruder to the process. Nanocrystal formulations are promising drug delivery systems owing to their ability to enhance the bioavailability and maintain the stability of poorly water-soluble drugs. However, conventional methods …

Preparation And Evaluation Of Valacyclovir Hydrochloride Ocular Inserts By Hot Melt Extrusion Technique, Gauri Shadambikar

Electronic Theses and Dissertations

The objective of the current study was to investigate the processability of Hot Melt Extrusion to formulate Ocular Inserts of Valacyclovir Hydrochloride and Evaluate its drug release in vitro and in vivo. Valacyclovir is the prodrug of Acyclovir, which is used in treatment of ocular keratitis and HSV infections. The bioavailability of the prodrug is better than the acyclovir and it is proved to permeate extensively through the corneal barrier. The polymer of choice was Klucel® Pharm MF and JF grades for the study. To optimize the formulation, different physical mixtures of the polymers and plasticizers (PEG 400 and Propylene …

Under-Reporting Of Adverse Drug Reactions To The Food & Drug Administration, James Alexander Lamb

Walden Dissertations and Doctoral Studies

This study examined the potential significant differences in the distribution of adverse drug reactions (ADRs) by reporter (consumer versus physician) and patient outcome at case and event level. This study also contains exploratory questions to evaluate reporting of ADRs by consumers versus physician by system organ class (SOC) and reporter demographics within the United States Food & Drug Administration Adverse Event Reporting System (FAERS). The theoretical foundation applied in this quantitative study was the social amplification of risk framework. Data from the second quarter of 2016 were obtained from FAERS, and a total of 87,807 ADR reports corresponding to 143,399 …

Aerosolized Surfactants: Formulation Development And Evaluation Of Aerosol Drug Delivery To The Lungs Of Infants, Susan Boc

Theses and Dissertations

The overall aim of this research project was to develop surfactant dry powder formulations and devices for efficient delivery of aerosol formulations to infants using the excipient enhanced growth (EEG) approach. Use of novel formulations and inline delivery devices would allow for more efficient treatment of infants suffering from neonatal respiratory distress syndrome and bronchiolitis.

A dry powder aerosol formulation has been developed using the commercial product, Survanta ® (beractant) and EEG technology to produce micrometer-sized hygroscopic particles. Spray drying and formulation parameters were initially determined with dipalmitoylphosphatidylcholine (DPPC, the dominant phospholipid in pulmonary surfactant), which produced primary particles 1 …

Pharmacy Driven Best Possible Admission Medication History At A Pediatric Institution, Damon Pabst, Charity Thompson, Brandon French, Brian O'Neal, Garret Matthews, Zeb Benner, Joshua Meade

Posters

No abstract provided.

Development Of Small Molecule Neuroprotectants, Ashley Boice

Theses and Dissertations

Neurodegenerative diseases are a class of conditions that lead to progressive atrophy of different parts of the central nervous system (CNS). These diseases lead to devastating clinical outcomes to patients and give rise to an enormous socio-economical burden on society.¹ One commonality among some of the most well-known neurodegenerative disorders, e.g. Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS), is neuroinflammation.^2-4 Neuroinflammation stems from interactions of the innate immune system with toxins and insults to the central nervous system. In the case of irremovable or chronic insults and toxins, this leads to chronic damaging …

Anticancer Effects Of Mansonone G Derivative On Human Colorectal Cancer Cells, Savinee Chanvijit

Chulalongkorn University Theses and Dissertations (Chula ETD)

Mansonone G (MG), 1,2-naphthoquinone, isolated from the heartwood of Mansonia gagei Drumm (Chan-Cha-Mod), exhibited several pharmacological effects including anti-bacterial, anti-estrogenic and anti-adipogenic effects. However, anticancer activity of MG and its derivatives on colorectal cancer (CRC) has never been investigated. Therefore, the objective of this study was to investigate the cytotoxic effect of MG and its derivatives and to determine the mechanism(s) underlying cytotoxicity of the most potent MG derivative on two CRC cell lines, HCT-116 cells carrying p53 wild-type and HT-29 cells carrying p53 mutant. In the present study, MG and its derivatives could inhibit viability of HCT-116 and HT-29 …

Physicochemical, Biopharmaceutical And Anti-Hepatocellular Carcinoma Properties Of Curcumin Diethyl Disuccinate, Chawanphat Muangnoi

Chulalongkorn University Theses and Dissertations (Chula ETD)

Curcumin ( Cur) has been reported for an anticancer activity by inducing apoptosis. However, the poor oral bioavailability of Cur due to chemical instability limits itself for further development as a chemotherapeutic agent. Previously, a succinate ester prodrug of Cur named as curcumin diethyl disuccinate (CurDD) has been designed and synthesized to enhance chemical stability of Cur. In this study, physicochemical and biopharmaceutical properties as well as in vitro and in vivo anti-hepatocellular carcinoma activities of CurDD were investigated and compared with those of Cur. CurDD could improve the stability of Cur in buffer pH 7.4 and simulated gastrointestinal fluids. …

Development Of In Situ Gel Containing Asiaticoside-Cyclodextrin Complex For Periodontal Tissue Regeneration, Hay Man Saung Hnin Soe

Chulalongkorn University Theses and Dissertations (Chula ETD)

Asiaticoside (AS) is active herbal compound isolated from Centella asiatica. It has the potential benefit in promoting type I collagen (COL I) synthesis and osteogenic differentiation in human periodontal ligament cells. However, it has low aqueous solubility which may hamper the bioavailability. Thus, the main objective of this study was to develop the thermoresponsive in situ gels containing AS by using cyclodextrin (CD). To determine the solubility enhancement of AS, phase-solubility profiles were investigated and revealed that CDs enhanced the aqueous solubility of AS. Hydroxypropyl-beta-CD (HPβCD) and sulfobutyl-ether-beta-CD (SBEβCD) were selected due to highly solubilization enhancement of AS. The mucoadhesive …

Topoisomerase I Inhibitory Compounds From The Roots Of Paphiopedilum Callosum, San Yoon Nwe

Chulalongkorn University Theses and Dissertations (Chula ETD)

Paphiopedilum callosum (Rchb.f.) Stein belongs to the Orchidaceae family. The phytochemistry and bioactivity of this plant have not been previously reported. In this study, the chromatographic separation of methanolic extract of P. callosum roots was bioassay-guided by a yeast cell-based assay. One new compound, 3′-hydroxy-2,6,5′-trimethoxystilbene (PC1) and five known compounds including 3′-hydroxy-2,5′-dimethoxystilbene (PC2), 3-methylethergalangin (PC3), galangin (PC4), 2,3′-dihydroxy-5,5′-dimethoxystilbene (PC5) and 2,3′-dihydroxy-5′-methoxystilbene (PC6) were isolated. The chemical structures of these isolated compounds were elucidated and identified on the basis of analysis spectroscopic (ESI-MS, NMR and IR), as well as comparison with those reported in the literature. Their topoisomerase I poison activity …

Development Of Novel Phenanthroline And Thiazole Orange Derived G-Quadruplex Ligands And Telomerase Inhibitors, Siwen Wang

University of the Pacific Theses and Dissertations

The end of the human chromosome is protected by telomeres which contain a special tandem guanine-rich DNA sequence, 5’-TTAGGG. The length of telomeres is shortened during cell replications, and its length limits the replication capacity of cells. Telomerase is over-expressed in 85–90% of cancer cells, responsible for extending the telomere length in cancer cells. Guanine-rich DNA sequence can self-assemble into unique G-quadruplex structures that interfere with the extension of telomeres by telomerase. Therefore, DNA G-quadruplex has recently received much attention because of its important regulatory functions in telomerase-mediated cancerization. The formation of G-quadruplex requires monovalent cations (Na+ and K+) or …

Determining The Role Played By Aryl Hydrocarbon Receptor (Ahr) In The Colon Carcinoma Tumor Model, Poonam Yakkundi

University of the Pacific Theses and Dissertations

Aryl hydrocarbon receptor (AHR), commonly known as an environmental sensor involved in the metabolism and elimination of xenobiotic substances, is also an important modulator in the development and functioning of the immune system. AHR expression is varied in the T cell subsets with the highest expression in T-helper 17 and T regulatory cells. Work from many researchers has suggested that AHR can act as a tumor promoter or a tumor suppressor depending on the tumor type. Our goal is to understand the role played by AHR in MC38 syngeneic colon carcinoma tumor model. In the absence of AHR, MC38 tumor …

Evaluation Of New Antimalarial Drug Combinations, Robert Tyrone Higginbotham

Honors Theses

Malaria is a disease that has affected people throughout the world for centuries and is still responsible for over 200 million clinical cases per year. While a number of developed countries have eradicated the disease, its prevalence in tropical regions poses a significant global health challenge. The disease is caused by the Plasmodium genus, an obligate, intracellular parasite that is carried by the female Anopheles mosquito. While there are effective antimalarial drugs in clinical use, Plasmodium's resilient nature has allowed it to develop resistance to multiple drugs. This fact makes it imperative to seek out novel drugs to combat resistant …

Evaluation Of Anthelmintic Properties And Toxicity Of Pure Compounds Isolated From Dalea Spp (Plantae, Fabaceae), Victoria Lh Mcpherson

All Master's Theses

Infecting upwards of a billion people worldwide, hookworm is one of the most prevalent parasitic infections affecting the world today. Those infected experience hookworm disease, characterized by severe anemia, which can lead to malnutrition, low birth weights, and physical and mental impairments. Currently, the benzimidazoles albendazole and mebendazole are used as the primary treatment; however, resistance to these drugs is emerging. Due to this resistance, finding new anthelmintic compounds active against hookworm is a priority. Previously, a pure compound isolated from Dalea ornata was identified as having strong anthelmintic activity when used against the hookworm Ancylostoma ceylanicum. This project …

Design And Analysis Of Curcumin Conjugated Poly(Beta-Amino Ester) Networks For Controlled Release In Oxidative Stress Environments, Carolyn T. Jordan

Theses and Dissertations--Chemical and Materials Engineering

Oxidative stress, the imbalance of free radical generation with antioxidant defenses, leads to cellular inflammation, apoptosis and cell death. This compromised environment results in debilitating diseases, such as oral mucositis (OM), atherosclerosis, and ischemia/reperfusion injury. Antioxidant therapeutics has been a proposed strategy to ameliorate these imbalances and maintain homeostatic environments. However, the success of these approaches, specifically curcumin, has been limited due to characteristics such as hydrophobicity and high reactivity when released as bolus doses to contest to oxidative stress induced diseases. The development of a controlled release system to aid in protection of the antioxidant capacity of curcumin, as …

The Development Of Microfluidic Devices For The Production Of Safe And Effective Non-Viral Gene Delivery Vectors, Jason Matthew Absher

Theses and Dissertations--Chemical and Materials Engineering

Including inherited genetic diseases, like lipoprotein lipase deficiency, and acquired diseases, such as cancer and HIV, gene therapy has the potential to treat or cure afflicted people by driving an affected cell to produce a therapeutic protein. Using primarily viral vectors, gene therapies are involved in a number of ongoing clinical trials and have already been approved by multiple international regulatory drug administrations for several diseases. However, viral vectors suffer from serious disadvantages including poor transduction of many cell types, immunogenicity, direct tissue toxicity and lack of targetability. Non-viral polymeric gene delivery vectors (polyplexes) provide an alternative solution but are …

Effect Of Compliance Of Enhanced Recovery After Surgery Protocols On Pain Control At A Community Medical Center, Julia Dickman Pharmd, Stacy Clore Pharmd, Bcps, Jamie Gaul Pharmd, Bcps, Sarah Fitzpatrick Pharmd, Bcps

Parkview Pharmacy Department

2018 ASHP Midyear Clinical Meeting / Anaheim, California / Poster 11-307

Objective: Determine the utilization of the Enhanced Recovery After Surgery (ERAS) protocols at Parkview Regional Medical Center (PRMC) • Assess the impact of both preoperative (pre-op) and postoperative (post-op) ERAS protocols on post-op pain management and nausea and vomiting in comparison to utilization of only pre-op or only post-op ERAS protocols.

Adherence To Guideline Recommended Treatment Of Copd In Discharged Patients Following An Acute Exacerbation, Kalee N. Swanson, Alissa Keillor Pharmd, Dustin D Linn Pharmd, Bcps, Bcccp

Parkview Pharmacy Department

Poster Presentation

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States, affecting more than 10 million Americans. Worldwide COPD is a disease of increasing public health importance as estimates suggest that COPD will rise from the fourth to the third most common cause of death by 2020. Increased exposure to risk factors and an aging population will attribute to even more patients with COPD. Adherence to guideline-recommended treatment regimens may decrease healthcare costs and improve patient outcomes. According to the GOLD guidelines, COPD pharmacotherapy recommendations are derived from the “ABCD” assessment tool, which …

Strategies For Compliance With Government Regulations In A Pharmaceutical Company, Charles Jagun

Walden Dissertations and Doctoral Studies

Pharmaceutical companies accrued fines of over $30 billion within 25 years because of noncompliance with regulations. Noncompliance with regulations results in fines and an adverse impact on company profitability. Some pharmaceutical company managers lack effective strategies to ensure overall company compliance with regulation. Based on complexity leadership theory, the purpose of this single case study was to explore strategies pharmaceutical company managers used to ensure compliance with regulatory requirements in Nigeria. The target population was functional managers purposely selected because they had successfully implemented strategies for compliance with the regulatory requirements in Nigeria. Data were collected through face-to-face and telephone …

Immunoglobulin Therapy And Primary Immunodeficient Patients' Health-Related Quality Of Life And Well-Being, Niedre Heckman

Walden Dissertations and Doctoral Studies

Individuals born with primary immune deficiency diseases (PIDD) have a dysfunctional immune system, and many are treated by lifelong injections of immunoglobulin therapy. Studies have shown that these patients have low health-related quality of life (HRQOL) and well-being (WB) and that these outcomes might be improved by the availability of therapy innovated according to preferences for fewer needle sticks or a shorter infusion time. Regulators at the U.S. Food and Drug Administration (FDA) have approved therapies innovated per these preferences. However, there is limited data demonstrating how these innovations impact HRQOL and WB. Using the biopsychosocial model, the purpose of …

Rational Design Of Peptides Binding Towards Human Pd-L1 Using Knob-Socket Model, Xingchen Zha

University of the Pacific Theses and Dissertations

Programmed death-ligand 1 (PD-L1) is a type 1 transmembrane protein that has been reported to play a vital role in mediating suppressed immunity. The interaction between PD-L1 and PD-1 delivers a negative signal that reduces the proliferation of these T cells and induces apoptosis at the same time. Antibodies that can block the Programmed death-ligand 1 (PD-L1) on tumor cells have been shown to alleviate cancer-induced immunosuppression. While antibodies have a great potential in various therapeutic uses, many drawbacks such as the high cost of production, huge molecular size, and poor permeability impose restrictions on the extensive use of full-length …

Bimetallic Complexes: The Fundamental Aspects Of Metal-Metal Interactions, Ligand Sterics And Application, Michael Bernard Pastor

University of the Pacific Theses and Dissertations

Metal containing complexes have been used to catalyze various organic transformations for the past few decades. The success of several mononuclear catalysts led to transition metal catalysts used in pharmaceuticals, environmental, and industrial processes. While mononuclear complexes have been used extensively, bimetallic systems have received far less attention. Bimetallic or polynuclear sites are commonly found in metalloenzymes that perform elegant transformation in biological systems, underlying their significance. Inorganic chemists take inspiration from nature and design model bimetallic complexes to further study this cooperativity effect. A bimetallic platform offers many structural and functional differences such as the identity of the metal …

Peptide-Drug Conjugate For Her2-Targeted Drug Delivery, Yan Wang

University of the Pacific Theses and Dissertations

Recent strategies for anticancer drug design have been focused on utilizing antibody as a drug or targeted moiety for targeted drug delivery. Antibody−drug conjugates (ADCs) have become a promising new class of targeted therapeutic agents for treatment of cancer. ADCs are designed to preferentially direct a cytotoxic drug to a cell-surface antigen recognized by an antibody. However, there are some challenges in developing ADCs, such as limited solid tumor penetration, high manufacturing costs and antibody-drug stoichiometry. Smaller molecules such as peptides have been shown to specifically bind to cancer related targets. These peptides can be used to form peptide-drug conjugates …