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Full-Text Articles in Medicine and Health Sciences

Promising Activity Of Anthemis Austriaca Jacq. On The Endometriosis Rat Model And Isolation Of Its Active Constituents, Mert Ilhan, Zulfiqar Ali, Ikhlas A. Khan, Hakkı Taştan, Esra Küpeli Akkol Sep 2019

Promising Activity Of Anthemis Austriaca Jacq. On The Endometriosis Rat Model And Isolation Of Its Active Constituents, Mert Ilhan, Zulfiqar Ali, Ikhlas A. Khan, Hakkı Taştan, Esra Küpeli Akkol

Faculty and Student Publications

© 2019, The Author(s). Heparin and heparan sulfate (Hp/HS) are linear complex glycosaminoglycans which are involved in diverse biological processes. The structural complexity brings difficulties in separation, making the study of structure-function relationships challenging. Here we present a separation method for Hp/HS oligosaccharide fractionation with cross-compatible solvent and conditions, combining size exclusion chromatography (SEC), ion-pair reversed phase chromatography (IPRP), and hydrophilic interaction chromatography (HILIC) as three orthogonal separation methods that do not require desalting or extensive sample handling. With this method, the final eluent is suitable for structure-function relationship studies, including tandem mass spectrometry and microarray printing. Our data indicate …


Δ9-Tetrahydrocannabinol Derivative-Loaded Nanoformulation Lowers Intraocular Pressure In Normotensive Rabbits, Pranjal S. Taskar, Akash Patil, Prit Lakhani, Eman Ashour, Waseem Gul, Mahmoud A. Elsohly, Brian Murphy, Soumyajit Majumdar Sep 2019

Δ9-Tetrahydrocannabinol Derivative-Loaded Nanoformulation Lowers Intraocular Pressure In Normotensive Rabbits, Pranjal S. Taskar, Akash Patil, Prit Lakhani, Eman Ashour, Waseem Gul, Mahmoud A. Elsohly, Brian Murphy, Soumyajit Majumdar

Faculty and Student Publications

No abstract provided.


Novel Targeting Approaches Of Nanoparticles For Anticancers Drug Delivery: A Focused Review, Yatri S. Patel, Nandita Das, Sudip Das Sep 2019

Novel Targeting Approaches Of Nanoparticles For Anticancers Drug Delivery: A Focused Review, Yatri S. Patel, Nandita Das, Sudip Das

Scholarship and Professional Work – COPHS

Nanoparticles have presented a new paradigm in anticancer drug delivery to reduce adverse effects and improve therapeutic outcomes. Nanoparticle surface properties and morphology significantly affect the drug delivery to tumors while passive targeting. Conjugations with hyaluronic acid, transferrin and aptamers have shown to be effective in active targeting of anticancer drugs to tumor tissues. This review presents an overview of some credible techniques of passive and active drug delivery to tumors.


Drug Safety Scientometrics Overview Highlights Public Health Issues, Philippe Gorry, Enrique Seoane-Vazquez Sep 2019

Drug Safety Scientometrics Overview Highlights Public Health Issues, Philippe Gorry, Enrique Seoane-Vazquez

Pharmacy Faculty Articles and Research

"Drug Safety (DS) also known as Pharmacovigilance, is the science of monitoring ADR (Cobert, 2012). Despite that DS has a social welfare function, it has not been the study of any scientometrics analysis... Our goal is to fill this gap by mapping the DS literature. This analysis might highlight some trends, the role of drug regulatory and firms in diffusing information, understand better some DS controversial events, help scholars in mastering pharmacovigilance literature, and it contribute to further development on literature-based discovery of ADR [adverse drug reactions] with the help of natural language processing."


Exploration Of The Inhibitory Properties Of The Nucleoside Antibiotic Salicyl-Ams And Analogues Targeting Siderophore Biosynthesis In Mycobacterium Tuberculosis, Glennon Bythrow Sep 2019

Exploration Of The Inhibitory Properties Of The Nucleoside Antibiotic Salicyl-Ams And Analogues Targeting Siderophore Biosynthesis In Mycobacterium Tuberculosis, Glennon Bythrow

Dissertations, Theses, and Capstone Projects

Mycobacterium tuberculosis (Mtb) is a resilient, obligate bacterial pathogen responsible for pulmonary tuberculosis disease (TB), that has upheld a significant impact on global public health throughout history. The World Health Organization (WHO) approximates nearly 10 million new TB cases arose in 2017 alone, accounting for 1.6 million deaths. There has been a notable rise in TB cases produced by multidrug‑resistant (MDR) and extensively drug-resistant (XDR) strains of Mtb. This, along with the intrinsic resistance of Mtb to many standard drugs and poor patient compliance, is deeply impacting global control of TB. Among the several strategies currently in …


Improving Recognition And Reporting Of Adverse Drug Reactions In The Nicu: A Quality Improvement Project., Betsy Cammack, Alexandra Oschman, Tamorah R. Lewis Md Phd Sep 2019

Improving Recognition And Reporting Of Adverse Drug Reactions In The Nicu: A Quality Improvement Project., Betsy Cammack, Alexandra Oschman, Tamorah R. Lewis Md Phd

Manuscripts, Articles, Book Chapters and Other Papers

Adverse drug reactions (ADRs) are under-recognized and under-reported in the Neonatal Intensive Care Unit (NICU) population, with up to 95% of all ADRs not reported. Compared with non-elderly adults, pediatric patients are 3 times more likely to experience an ADR, with varying rates from 0.6% to 16.8%. The Children's Mercy NICU has an ADR rate of 0.29% (2015). This high rate presents an opportunity to increase recognition and reporting, and improve characterization of ADRs in the NICU.

Methods: The primary aim of this quality improvement project was for 70% of patients who received specified medications (indomethacin, dexmedetomidine, fentanyl, lorazepam, dexamethasone, …


Evaluation Of Prescribing Patterns Of Long-Acting Injectable Antipsychotics Within A Community Health System., Jared Netley Pharmd, Mpa, Bcps, Jamie Gaul Pharmd, Bcps, Chelsea L Ferguson Pharmd Sep 2019

Evaluation Of Prescribing Patterns Of Long-Acting Injectable Antipsychotics Within A Community Health System., Jared Netley Pharmd, Mpa, Bcps, Jamie Gaul Pharmd, Bcps, Chelsea L Ferguson Pharmd

Parkview Pharmacy Department

PURPOSE/BACKGROUND: Long-acting injectable antipsychotics (LAIAs) are used in the management of schizophrenia, bipolar disorder, and related psychiatric conditions. The efficacy of LAIAs has been established in randomized controlled trials; however, usage of LAIAs outside of randomized controlled trials may not correlate to naturalistic prescribing habits. The purpose of this analysis was to evaluate the prescribing patterns of LAIAs within our health system and identify any inconsistencies between medications' published labeling information and clinical practice.

METHODS/PROCEDURES: All patients who received a LAIA at the time of the analysis were included for review. Areas of inconsistency between the prescribed LAIA and each …


Modelling In Vitro Dissolution And Release Of Sumatriptan Succinate From Polyvinylpyrrolidone-Based Microneedles Aided By Iontophoresis, James Paul Ronnander Aug 2019

Modelling In Vitro Dissolution And Release Of Sumatriptan Succinate From Polyvinylpyrrolidone-Based Microneedles Aided By Iontophoresis, James Paul Ronnander

Dissertations

A novel dissolving microneedle array system is developed to investigate permeation of a sumatriptan succinate formulations through the skin aided by iontophoresis. Three formulations consisting of hydrophilic, positively charged drug molecules encapsulated in a water-soluble biologically suitable polymer, polyvinylpyrrolidone (PVP), have been accepted by the U.S. Food and Drug Administration (FDA). The microneedle systems are fabricated with 600 pyramid-shaped needles, each 500 µm tall, on a 0.785-cm2 circular array. In vitro transdermal studies with minipig skin and vertical Franz diffusion cells show > 68% permeation of sumatriptan over a 24-hour period. A combination of microneedle and electrical current density ranging …


Roles Of Surfactant And Binary Polymers On Dissolution Enhancement Of Bcs Ii Drugs From Nanocomposites And Amorphous Solid Dispersions, Md Mahbubur Rahman Aug 2019

Roles Of Surfactant And Binary Polymers On Dissolution Enhancement Of Bcs Ii Drugs From Nanocomposites And Amorphous Solid Dispersions, Md Mahbubur Rahman

Dissertations

Drug nanocomposites and amorphous solid dispersions (ASDs) are two major formulation platforms used for the bioavailability enhancement of BCS Class II drugs. The major drawback of nanocomposites is their inability to attain high drug supersaturation during in vitro (<50% relative supersaturation) and in vivo dissolution. On the other hand, formulating an amorphous solid dispersion (ASD) with high drug loading (>20%) that releases drug rapidly, while generating and maintaining high supersaturation over at least three hours is challenging. The goal of this thesis is to develop a fundamental understanding of the impact of anionic surfactants–polymers on in vitro drug release from nanocomposites and ASDs, while addressing the above challenges. To achieve this goal, the following objectives are set: (1) compare griseofulvin …


The Role Of Using Formative Assessments In Problem-Based Learning: A Health Sciences Education Perspective, Kristi W. Kelley, Julaine M. Fowlin, Andrew A. Tawfik, Max C. Anderson Aug 2019

The Role Of Using Formative Assessments In Problem-Based Learning: A Health Sciences Education Perspective, Kristi W. Kelley, Julaine M. Fowlin, Andrew A. Tawfik, Max C. Anderson

Interdisciplinary Journal of Problem-Based Learning

Practitioners in the field of pharmacy are often confronted with ill-structured problems. Specifically, pharmacists are tasked with making patient-specific recommendations that are both safe and effective, which requires combining knowledge from the biomedical, behavioral, and pharmaceutical sciences. Given the dynamic nature of pharmacy as a profession, the field has begun to explore learning strategies that go beyond mere content coverage to strategies that better support higher-order learning outcomes. One of these approaches is problem-based learning (PBL). While studies have focused on how to support PBL to improve learning outcomes, the role of assessment is often overlooked. Further exploration is thus …


Direct Measurement Of Performance: A New Era In Antimicrobial Stewardship, Majdi N. Al-Hasan, Hana Rac Winders, P. Brandon Bookstaver, Julie Ann Justo Aug 2019

Direct Measurement Of Performance: A New Era In Antimicrobial Stewardship, Majdi N. Al-Hasan, Hana Rac Winders, P. Brandon Bookstaver, Julie Ann Justo

Faculty Publications

Penicillin allergies are among of the most commonly reported allergies, yet only 10% of these patients are truly allergic. This leads to potential inadvertent negative consequences for patients and makes treatment decisions challenging for clinicians. Thus, allergy assessment and penicillin skin testing (PST) are important management strategies to reconcile and clarify labeled penicillin allergies. While PST is more common in the inpatient setting where the results will immediately impact antibiotic management, this process is becoming of increasing importance in the outpatient setting. PST in the outpatient setting allows clinicians to proactively de-label and educate patients accordingly so beta-lactam antibiotics may …


Penicillin Allergy Skin Testing In The Inpatient Setting, Julie Ann Justo, Wesley D. Kufel, Lisa Avery, P. Brandon Bookstaver Aug 2019

Penicillin Allergy Skin Testing In The Inpatient Setting, Julie Ann Justo, Wesley D. Kufel, Lisa Avery, P. Brandon Bookstaver

Faculty Publications

The consequences of a documented penicillin allergy in the medical record are especially troublesome in acutely ill, hospitalized patients. A penicillin allergy label may lead to alternative or second line therapies resulting in adverse drug events, negative clinical outcomes and increased costs. Reconciling penicillin allergies is a necessity to facilitate early, optimal therapy and is a shared responsibility among the healthcare team. Penicillin skin testing (PST) has been utilized successfully in hospitalized patients to de-label erroneous penicillin allergies and optimize antibiotic therapy. This targeted review aims to discuss the practical development and implementation of PST in the inpatient setting. This …


Penicillin Allergy Skin Testing In The Inpatient Setting, Julie Ann Justo, Wesley D. Kufel, Lisa M. Avery, P. Brandon Bookstaver Aug 2019

Penicillin Allergy Skin Testing In The Inpatient Setting, Julie Ann Justo, Wesley D. Kufel, Lisa M. Avery, P. Brandon Bookstaver

Pharmacy Faculty/Staff Publications

The consequences of a documented penicillin allergy in the medical record are especially troublesome in acutely ill, hospitalized patients. A penicillin allergy label may lead to alternative or second line therapies resulting in adverse drug events, negative clinical outcomes and increased costs. Reconciling penicillin allergies is a necessity to facilitate early, optimal therapy and is a shared responsibility among the healthcare team. Penicillin skin testing (PST) has been utilized successfully in hospitalized patients to de-label erroneous penicillin allergies and optimize antibiotic therapy. This targeted review aims to discuss the practical development and implementation of PST in the inpatient setting. This …


Resident Physicians’ Perceptions Of Ambulatory Care Pharmacy, Ashley Meredith, Darin Ramsey, Andrew Schmelz, Rachel Berglund Aug 2019

Resident Physicians’ Perceptions Of Ambulatory Care Pharmacy, Ashley Meredith, Darin Ramsey, Andrew Schmelz, Rachel Berglund

Scholarship and Professional Work – COPHS

Background: Physicians' acceptance of clinical pharmacy services is dependent on exposure to those services, with use increasing as resident physicians progress through their training. Resident physicians train within environments that have a multidisciplinary teaching and clinical care approach, working closely with other healthcare professionals. Ambulatory care pharmacists are increasingly working with resident physicians in clinic settings as part of the multidisciplinary team, and identification of resident physicians’ perceptions may influence future collaboration.

Objective: The objective of this research is to evaluate the perception of ambulatory care clinical pharmacy services from the perspective of resident physicians.

Methods: A statewide network of …


Resident Physicians’ Perceptions Of Ambulatory Care Pharmacy, Ashley H. Meredith, Darin Ramsey, Andrew Schmelz, Rachel Berglund Aug 2019

Resident Physicians’ Perceptions Of Ambulatory Care Pharmacy, Ashley H. Meredith, Darin Ramsey, Andrew Schmelz, Rachel Berglund

Department of Pharmacy Practice Faculty Publications

Background: Physicians' acceptance of clinical pharmacy services is dependent on exposure to those services, with use increasing as resident physicians progress through their training. Resident physicians train within environments that have a multidisciplinary teaching and clinical care approach, working closely with other healthcare professionals. Ambulatory care pharmacists are increasingly working with resident physicians in clinic settings as part of the multidisciplinary team, and identification of resident physicians’ perceptions may influence future collaboration.

Objective: The objective of this research is to evaluate the perception of ambulatory care clinical pharmacy services from the perspective of resident physicians.

Methods: A statewide network of …


Synthesis Of Betulinic Acid Via Baylis-Hillman Reaction, Sai Krishna Kommineni Aug 2019

Synthesis Of Betulinic Acid Via Baylis-Hillman Reaction, Sai Krishna Kommineni

Theses and Dissertations

Betulin is readily isolated from the bark of birch trees using simple extraction techniques and this molecule as well as its derivatives (eg. betulinic acid) exhibit impressive levels of biological activity. While it is naturally available and shows selective toxicity towards certain cancers, betulin suffers from a general lack of solubility in aqueous conditions. In this regard, we took up a project involving the synthesis of conjugates of betulin with improved solubility characteristics and we were able to identify a series of compounds that showed cytotoxicity against breast and pancreatic cancer cells.

This thesis describes our efforts on the development …


No Meaningful Drug Interactions With Doravirine, Lamivudine And Tenofovir Disoproxil Fumarate Co-Administration., Matt S. Anderson, Jocelyn Gilmartin, Li Fan, Ka Lai Yee, Walter K. Kraft, Ilias Triantafyllou, Christina Reitmann, Ying Guo, Rachael Liu, Marian Iwamoto Aug 2019

No Meaningful Drug Interactions With Doravirine, Lamivudine And Tenofovir Disoproxil Fumarate Co-Administration., Matt S. Anderson, Jocelyn Gilmartin, Li Fan, Ka Lai Yee, Walter K. Kraft, Ilias Triantafyllou, Christina Reitmann, Ying Guo, Rachael Liu, Marian Iwamoto

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor available as a single tablet and a three-drug combination with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) to treat HIV-1 infection. These analyses assessed pharmacokinetic (PK) interactions with co-administration.

METHODS: Two trials were conducted. Study 1: two-period, fixed-sequence; 8 healthy participants; Period 1, DOR 100 mg followed by ≥7-day washout; Period 2, TDF 300 mg once daily for 18 days, co-administration of DOR 100 mg on day 14. Study 2: three-period, crossover, 15 healthy participants; Treatment A, DOR 100 mg; Treatment B, 3TC 300 mg + TDF 300 mg; Treatment …


Development Of Functionalized Imidazoles As Potential Therapeutical Agents, Drew Christopher Morgan Aug 2019

Development Of Functionalized Imidazoles As Potential Therapeutical Agents, Drew Christopher Morgan

Theses and Dissertations

Imidazoles are heterocyclic small molecules that play a major role in medicinal chemistry and drug discovery. There are several drugs in the market which contain imidazoles as the pharmacophore. Metronidazole, an imidazole containing compound, is a prominent antibiotic and antiprotozoal medication used for the treatment of a variety of infections such as amoebiasis, trichomoniasis, bacterial vaginosis, etc. The current work involves the synthesis of small molecule libraries of imidazoles derived from metronidazole using Baylis-Hillman (BH) reaction. BH reaction is a carbon-carbon bond forming reaction and involves the coupling of aldehydes or imines with activated alkenes such as acrylates, acrolein, or …


The Power Of Pharmacist-To-Pharmacist Handoffs During Transitions Of Care, Jessica Wooster, Laressa Bethishou Aug 2019

The Power Of Pharmacist-To-Pharmacist Handoffs During Transitions Of Care, Jessica Wooster, Laressa Bethishou

Pharmacy Faculty Articles and Research

"Hospital readmissions are often medication-related and potentially preventable. Pharmacists can play a vital role in improving medication outcomes during transitions of care (TOC). Although numerous TOC practice models have been described, it remains unclear what practices will promote optimal continuity of care."


Functionalized Heterocyclics As Potential Therapeutics, Anupama Indukuri Aug 2019

Functionalized Heterocyclics As Potential Therapeutics, Anupama Indukuri

Theses and Dissertations

Heterocyclic compounds play an important role in pharmaceutical drug development. Several natural products and biologically active compounds contain heterocyclic motifs in them. Multicomponent coupling reactions offer an excellent platform for the synthesis of diverse libraries of heterocyclic compounds. We have been working on the synthesis of novel heterocyclic small molecules utilizing reactions such as Baylis-Hillman reaction, Passerini reaction, Click reaction, reductive amination aldol condensation, etc.

In the current project, we prepared three series of heterocyclic compounds using Passerini and Baylis-Hillman reactions as key steps. Owing to the importance of heterocyclic chemistry in drug discovery and the ease of synthesis, the …


N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She Aug 2019

N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and β1-integrin receptors, resulting in Met/β1-integrin co-internalization and co-accumulation on endosomes. This provides persistent …


Development Of An Imaging Analysis Algorithm For Fluorescence-Based High Content Screening In Parkinson’S Disease, Ryan Arlinghaus Aug 2019

Development Of An Imaging Analysis Algorithm For Fluorescence-Based High Content Screening In Parkinson’S Disease, Ryan Arlinghaus

The Journal of Purdue Undergraduate Research

No abstract provided.


A Pharmacological Model Of Trpa1-Mediated Nociception In Zebrafish For Therapeutic Discovery, Emre Coskun Aug 2019

A Pharmacological Model Of Trpa1-Mediated Nociception In Zebrafish For Therapeutic Discovery, Emre Coskun

The Journal of Purdue Undergraduate Research

No abstract provided.


August 2019, Randy Curry, Cindy Brooks Aug 2019

August 2019, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy


Rna-Based Compositions And Adjuvants For Prophylactic And Therapeutic Treatment, Peixuan Guo, Hui Li, Emil F. Khisamutdinov, Daniel L. Jasinski Aug 2019

Rna-Based Compositions And Adjuvants For Prophylactic And Therapeutic Treatment, Peixuan Guo, Hui Li, Emil F. Khisamutdinov, Daniel L. Jasinski

Pharmaceutical Sciences Faculty Patents

The present invention is directed towards an artificial RNA nano structure comprising multiple external strands of RNA, each external strand comprising about 40-50 nucleotides; one internal strand of RNA comprising more than about 50 nucleotides; the internal strands and external strands assembled to form a triangle nanostructure, a square nanostructure, or a polygon nanostructure and a pRNA three-way junction (3WJ) motif at each vertex of the nanostructure. Such nanostructure can be provided in a composition together with an adjuvant for use in inducing the production of high affinity neutralizing antibodies or inhibitory antibodies, inducing the production of cytokines, inducing an …


The Place Of Arbs In Heart Failure Therapy: Is Aldosterone Suppression The Key?, Uma Markan, Samhitha Pasupuleti, Celina M. Pollard, Arianna Perez Bhs Student, Beatrix Aukszi, Anastasios Lymperopoulos Aug 2019

The Place Of Arbs In Heart Failure Therapy: Is Aldosterone Suppression The Key?, Uma Markan, Samhitha Pasupuleti, Celina M. Pollard, Arianna Perez Bhs Student, Beatrix Aukszi, Anastasios Lymperopoulos

Chemistry and Physics Faculty Articles

Since the launch of the first orally available angiotensin II (AngII) type 1 receptor (AT1R) blocker (ARB) losartan (Cozaar) in the late 1990s, the class of ARBs (or ‘sartans’, short for Angiotensin-RecepTor-ANtagonistS) quickly expanded to include candesartan, eprosartan, irbesartan, valsartan, telmisartan, and olmesartan. All ARBs have high affinity for the AT1 receptor, expressed in various tissues, including smooth muscle cells, heart, kidney, and brain. Since activation of AT1R, the target of these drugs, leads, among other effects, to vascular smooth muscle cell growth, proliferation and contraction, activation of fibroblasts, cardiac hypertrophy, aldosterone secretion from the …


Amorphous Solid Dispersion Formation Via Solvent Granulation – A Case Study With Ritonavir And Lopinavir, Niraj S. Tirasi, Sonal Bhujbal, Qi Tony Zhou, Lynne Taylor Aug 2019

Amorphous Solid Dispersion Formation Via Solvent Granulation – A Case Study With Ritonavir And Lopinavir, Niraj S. Tirasi, Sonal Bhujbal, Qi Tony Zhou, Lynne Taylor

Department of Industrial and Physical Pharmacy Faculty Publications

Herein, we evaluate the potential of using a simple solvent granulation process to prepare a binary drug amorphous solid dispersion (ASD) containing two anti-HIV drugs, ritonavir and lopinavir. The drugs were granulated onto a mixture of lactose and microcrystalline cellulose, followed by drying to remove the solvent. The resultant granules were characterized and each drug was found to be X-ray amorphous. No crystallization was observed following storage for 1 month under accelerated stability conditions (40 °C and 75% relative humidity). The dissolution behavior of the compacted granules was compared with the marketed formulation. The dissolution rate of ritonavir was found …


Design And Synthesis Of Pyrimidine Based Heterocycles As Potential Anti-Cancer Agents With Combination Chemotherapeutic Potential Or Targeted One Carbon Metabolism Inhibition And Anti-Opportunistic Agents, Arpit Doshi Aug 2019

Design And Synthesis Of Pyrimidine Based Heterocycles As Potential Anti-Cancer Agents With Combination Chemotherapeutic Potential Or Targeted One Carbon Metabolism Inhibition And Anti-Opportunistic Agents, Arpit Doshi

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic, bicyclic and tricyclic pyrimidine-based heterocycles as a) single agents with combination chemotherapy potential having dual antiangiogenic effects and cytotoxic effects or b) one-carbon metabolism inhibitors for targeted tumor therapy; or c) selective Pneumocystis jirovecii (pj) dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization or thymidylate synthase as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), epidermal growth …


A Quantitative Study Of Drug Recrystallization In Drug-In-Adhesive Transdermal Patches Using Vibrational Spectroscopy, Yi Li Aug 2019

A Quantitative Study Of Drug Recrystallization In Drug-In-Adhesive Transdermal Patches Using Vibrational Spectroscopy, Yi Li

Electronic Theses and Dissertations

Drug-in-adhesive (DIA) transdermal patches are an important type of transdermal drug delivery system (TDDS). The drugs used in the DIA system are frequently present in metastable forms, such as amorphous solids or supercooled liquids. These drug states are thermodynamically unstable and tend to undergo recrystallization. Recrystallization of the active pharmaceutical ingredient can adversely affect the efficacy of transdermal products. This dissertation demonstrates a systematic approach to quantify the crystalline content of the API in DIA systems. This approach uses a novel method of preparing calibration standards and a spectroscopic method to reliably predict crystalline content in DIA patches. Spectroscopic tools, …


Dual Inhibition Of The Pi3k/Akt And Mek5/Erk5 Pathways For The Treatment Of Breast Cancer, Thomas Douglas Wright Aug 2019

Dual Inhibition Of The Pi3k/Akt And Mek5/Erk5 Pathways For The Treatment Of Breast Cancer, Thomas Douglas Wright

Electronic Theses and Dissertations

Breast cancer is a heterogeneous disease state with several challenging frontiers. In particular, aberrations in the Phosphoinositide-3-kinase (PI3K) and Mitogen Activated Protein Kinase (MAPK) pathways have been linked to increased breast cancer proliferation and survival. It has been proposed that these survival characteristics are enhanced through compensatory signaling and crosstalk mechanisms. New evidence suggests that MEK5/ERK5, a member of the MAPK family, is a crucial component in the proliferation and survival of several aggressive cancers. We hypothesize that inhibiting both PI3K/Akt and MEK5/ERK5 pathways will decrease cell viability while maintaining limited collateral toxicity. In this study, we examined the effects …