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Pharmacy and Pharmaceutical Sciences

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Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Purification And Characterization Of A Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Meshal Nazeer, Humera Waheed, Maria Saeed, Saman Yousuf Ali, M. Iqbal Choudhary, Zaheer Ul-Haq, Aftab Ahmed Mar 2019

Purification And Characterization Of A Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Meshal Nazeer, Humera Waheed, Maria Saeed, Saman Yousuf Ali, M. Iqbal Choudhary, Zaheer Ul-Haq, Aftab Ahmed

Pharmacy Faculty Articles and Research

Ajwain (Trachyspermum ammi) belongs to the family Umbelliferae, is commonly used in traditional, and folk medicine due to its carminative, stimulant, antiseptic, diuretic, antihypertensive, and hepatoprotective activities. Non-specific lipid transfer proteins (nsLTPs) reported from various plants are known to be involved in transferring lipids between membranes and in plants defense response. Here, we describe the complete primary structure of a monomeric non-specific lipid transfer protein 1 (nsLTP1), with molecular weight of 9.66 kDa, from ajwain seeds. The nsLTP1 has been purified by combination of chromatographic techniques, and further characterized by mass spectrometry, and Edman degradation. The ajwain nsLTP1 is ...


Synthesis, Biological Evaluation And Molecular Modeling Studies Of Novel Chromone/Aza-Chromone Fused Α-Aminophosphonates As Src Kinase Inhibitors, S. Bapat, N. Viswanadh, M. Mujahid, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, M. Karthikeyan, M. Muthukrishnan, Renu Vyas Feb 2019

Synthesis, Biological Evaluation And Molecular Modeling Studies Of Novel Chromone/Aza-Chromone Fused Α-Aminophosphonates As Src Kinase Inhibitors, S. Bapat, N. Viswanadh, M. Mujahid, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, M. Karthikeyan, M. Muthukrishnan, Renu Vyas

Pharmacy Faculty Articles and Research

A series of novel chromone/aza-chromone fused α-aminophosphonate derivatives were synthesized in good yields using silica chloride as the catalyst. All the synthesized compounds were tested for their c-Src kinase inhibitory activity. Aza-chromone compound showed Src kinase inhibition with an IC50 value of 15.8 µM. The compounds were subjected to molecular docking and dynamics simulations to study the atomic level interactions with an unphosphorylated proto-oncogenic tyrosine protein kinase Src (PDB code 1Y57) as well as phosphorylated tyrosine protein kinase Src (PDB code 2H8H). Docking and molecular dynamic results revealed phosphorylated Src tyrosine kinase protein better results than unphosphorylated tyrosine ...


Green Chemistry Oxidative Modification Of Peptoids Utilizing Bleach And Tempo, Jesse Leland Roberts Dec 2017

Green Chemistry Oxidative Modification Of Peptoids Utilizing Bleach And Tempo, Jesse Leland Roberts

Theses and Dissertations

Biotherapeutic drugs, derived from biological molecules such as proteins and DNA, are becoming an integral and exceptionally critical aspect of modern medicine. Compared to common pharmaceutical drugs, biotherapeutics are much larger in size and have greater target specificity, allowing them to treat many chronic diseases ranging from cancer to rheumatoid arthritis. The major issue with protein based therapeutics is that they readily undergo proteolysis, or enzymatic degradation, when administered through subcutaneous injections. Traditionally, biotherapeutic modification procedures have centered on the use of PEG derivatives. This process, called PEGylation, is unfavorable due to the increases in molecular weights of the proteins ...


Ensemble-Based Modeling And Rigidity Decomposition Of Allosteric Interaction Networks And Communication Pathways In Cyclin-Dependent Kinases: Differentiating Kinase Clients Of The Hsp90-Cdc37 Chaperone, Gabrielle Stetz, Amanda Tse, Gennady M. Verkhivker Nov 2017

Ensemble-Based Modeling And Rigidity Decomposition Of Allosteric Interaction Networks And Communication Pathways In Cyclin-Dependent Kinases: Differentiating Kinase Clients Of The Hsp90-Cdc37 Chaperone, Gabrielle Stetz, Amanda Tse, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The overarching goal of delineating molecular principles underlying differentiation of protein kinase clients and chaperone-based modulation of kinase activity is fundamental to understanding activity of many oncogenic kinases that require chaperoning of Hsp70 and Hsp90 systems to attain a functionally competent active form. Despite structural similarities and common activation mechanisms shared by cyclin-dependent kinase (CDK) proteins, members of this family can exhibit vastly different chaperone preferences. The molecular determinants underlying chaperone dependencies of protein kinases are not fully understood as structurally similar kinases may often elicit distinct regulatory responses to the chaperone. The regulatory divergences observed for members of CDK ...


Progress Toward The Development Of A "Catch/Release" Strategy For Isolating Salvinorin A, From Plant Materails Including Microwave Promotion, Douglas Armstrong, Logan Smith Oct 2017

Progress Toward The Development Of A "Catch/Release" Strategy For Isolating Salvinorin A, From Plant Materails Including Microwave Promotion, Douglas Armstrong, Logan Smith

Faculty Scholarship – Chemistry

We are investigating using the Diels-Alder and retro-Diels-Alder reactions as a potential “catch/release” strategy for isolating Salvinorin A from plant samples (Salvia divinorum), hopefully to improve the current method, which is very long and laborious. Salvinorin A has analgesic activity by activating the kappa opioid receptor, not the mu receptor, and thus it has potential for being developed into a non-addicting analgesic.


Cellular And Molecular Targets Of Menthol Actions, Murat Oz, Eslam El Nebrisi, Keun-Hang Susan Yang, Frank Christopher Howarth, Lina T. Al Kury Jul 2017

Cellular And Molecular Targets Of Menthol Actions, Murat Oz, Eslam El Nebrisi, Keun-Hang Susan Yang, Frank Christopher Howarth, Lina T. Al Kury

Mathematics, Physics, and Computer Science Faculty Articles and Research

Menthol belongs to monoterpene class of a structurally diverse group of phytochemicals found in plant-derived essential oils. Menthol is widely used in pharmaceuticals, confectionary, oral hygiene products, pesticides, cosmetics, and as a flavoring agent. In addition, menthol is known to have antioxidant, anti-inflammatory, and analgesic effects. Recently, there has been renewed awareness in comprehending the biological and pharmacological effects of menthol. TRP channels have been demonstrated to mediate the cooling actions ofmenthol. There has been new evidence demonstrating thatmenthol can significantly influence the functional characteristics of a number of different kinds of ligand and voltage-gated ion channels, indicating that at ...


Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer Jul 2017

Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a ...


Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer Jun 2017

Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1' and S2' subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency ...


Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer May 2017

Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1' and S2' subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency ...


Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer Apr 2017

Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a ...


Naloxone Therapy In Opioid Overdose Patients: Intranasal Or Intravenous?, Leiah Carney Jan 2017

Naloxone Therapy In Opioid Overdose Patients: Intranasal Or Intravenous?, Leiah Carney

Natural Sciences Poster Sessions

This slide presentation for the Natural Science Poster Session at Parkland College describes the chemical makeup and effect of Naloxone, an opioid antagonist used in the treatment opioid overdose and summarizes a study comparing intravenous and intranasal delivery methods. Concludes that although there are conflicting studies, evidence supports intranasal delivery.


Development Of Diverse Size And Shape Rna Nanoparticles And Investigation Of Their Physicochemical Properties For Optimized Drug Delivery, Daniel L. Jasinski Jan 2017

Development Of Diverse Size And Shape Rna Nanoparticles And Investigation Of Their Physicochemical Properties For Optimized Drug Delivery, Daniel L. Jasinski

Theses and Dissertations--Pharmacy

RNA nanotechnology is an emerging field that holds great promise for advancing drug delivery and materials science. Recently, RNA nanoparticles have seen increased use as an in vivo delivery system. RNA was once thought to have little potential for in vivo use due to biological and thermodynamic stability issues. However, these issues have been solved by: (1) Finding of a thermodynamically stable three-way junction (3WJ) motif; (2) Chemical modifications to RNA confer enzymatic stability in vivo; and (3) the finding that RNA nanoparticles exhibit low immunogenicity in vivo.

In vivo biodistribution and pharmacokinetics are affected by the physicochemical properties, such ...


Design, Synthesis, And Evaluation Of Dasatinib-Amino Acid And Dasatinib-Fatty Acid Conjugates As Protein Tyrosine Kinase Inhibitors, Rakesh Tiwari, Alex Brown, Neda Sadeghiani, Amir Nasrolahi Shirazi, Jared Bolton, Amanda Tse, Gennady M. Verkhivker, Keykavous Parang, Gongqin Sun Nov 2016

Design, Synthesis, And Evaluation Of Dasatinib-Amino Acid And Dasatinib-Fatty Acid Conjugates As Protein Tyrosine Kinase Inhibitors, Rakesh Tiwari, Alex Brown, Neda Sadeghiani, Amir Nasrolahi Shirazi, Jared Bolton, Amanda Tse, Gennady M. Verkhivker, Keykavous Parang, Gongqin Sun

Pharmacy Faculty Articles and Research

Derivatives of dasatinib were synthesized via esterification with 25 carboxylic acids including amino acids and fatty acids by extending the inhibitor to interact with more diverse sites and to improve specificity. Dasatinib-L-arginine derivative (Das-R, 7) was the most potent of the inhibitors tested with IC50 values of 4.4 nM, <0.25 nM, and <0.45 nM against Csk, Src, and Abl kinases, respectively. The highest selectivity ratio obtained in our study, 91.4 Csk/Src belonged to compound 18 (Das-C10) with an IC50 of 3.2 μM for Csk compared to 35 nM for Src. Furthermore, many compounds displayed increased selectivity toward Src, as compared with Abl. Compounds 15 (Das-E) and 13 (Das-C) demonstrated the largest gains (10.2 and 10.3 Abl/Src IC50 ratios). Das-R (IC50 = 2.06 μM) was significantly more potent than Das (IC50 = 26.3 μM) against Panc-1 cells while they both showed an IC50 < 51.2 pM against BV-173 and K562 cells. Molecular modeling and binding free energy simulations revealed a good agreement with the experimental results and rationalized differences in selectivity of the studied compounds. Integration of experimental and computational approaches in the design and biochemical screening of dasatinib derivatives facilitated rational engineering and diversification of dasatinib scaffold, providing useful insights into mechanisms of kinase selectivity.


Theoretical And Experimental Analysis Of The Antioxidant And Anti-Amyloid Features Of Synthetic Resveratrol Mimics, William Horton, Anne Kokel, Fanni Török, Chris Tran, Marianna Török, Bela Török May 2016

Theoretical And Experimental Analysis Of The Antioxidant And Anti-Amyloid Features Of Synthetic Resveratrol Mimics, William Horton, Anne Kokel, Fanni Török, Chris Tran, Marianna Török, Bela Török

UMass Center for Clinical and Translational Science Research Retreat

Diaryl hydrazones, possessing similar structure to the popular red wine antioxidant resveratrol, have been previously identified as multitarget compounds interfering with several processes associated with the pathogenesis of Alzheimer’s disease (AD). These compounds exhibited particularly strong inhibition of the amyloid beta (A) peptide self-assembly, including blocking the formation of fibrils and oligomers, species that are widely accepted to be neurotoxic. The molecules were also powerful free radical scavengers and thus have a potential to defend against oxidative stress.

In order to learn more about the mode of action of the compounds, theoretical and experimental studies have been carried out ...


Crystal Protein Cry5b As A Novel And Powerful Anthelmintic, David Koch, Zeynep Mirza, Yan Hu, Thanh-Thanh Nguyen, Gary R. Ostroff, Raffi V. Aroian May 2016

Crystal Protein Cry5b As A Novel And Powerful Anthelmintic, David Koch, Zeynep Mirza, Yan Hu, Thanh-Thanh Nguyen, Gary R. Ostroff, Raffi V. Aroian

UMass Center for Clinical and Translational Science Research Retreat

Soil-transmitted helminths (STHs), most notably, hookworms, whipworms, and Ascaris, are nematodes that infect more than 1.5 billion of the poorest people and are amongst the leading causes of morbidity worldwide. Only two classes of de-worming drugs (anthelmintics) are available for treatment, and only one is commonly used in mass drug administrations. New anthelmintics are urgently needed to overcome emerging resistance and to produce higher cure rates. Crystal (Cry) proteins, in particular Cry5B, made by Bacillus thuringiensis (Bt) are promising new candidates. Cry5B has excellent anthelmintic properties against many free-living and parasitic nematodes, including in vivo efficacy against multiple STH ...


Development And Validation Of A Sensitive Uplc-Ms/Ms Method For The Quantitation Of [13c]Sucrose In Rat Plasma, Blood, And Brain: Its Application To The Measurement Of Blood-Brain Barrier Permeability, Mohammad K. Miah, Ulrich Bickel, Reza Mehvar Feb 2016

Development And Validation Of A Sensitive Uplc-Ms/Ms Method For The Quantitation Of [13c]Sucrose In Rat Plasma, Blood, And Brain: Its Application To The Measurement Of Blood-Brain Barrier Permeability, Mohammad K. Miah, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Accurate and reproducible measurement of blood-brain barrier (BBB) integrity is critical in the assessment of the pathophysiology of the central nervous system disorders and in monitoring therapeutic effects. The widely-used low molecular weight marker [14C]sucrose is non-specific in the absence of chromatographic separation. The purpose of this study was to develop and validate a sensitive and reproducible LC-MS/MS method for the analysis of stable isotopemodified [13C12]sucrose in brain, plasma, and blood to determine BBB permeability to sucrose. After addition of internal standard (IS, [13C6]sucrose), the marker and IS were recovered from diluted rat blood, plasma, and ...


Discovery Of Small Molecule Fcγriia Antagonists, Michael Thai Trung King Nov 2015

Discovery Of Small Molecule Fcγriia Antagonists, Michael Thai Trung King

PhD theses

Antibodies are Y-shaped proteins that are secreted by B-cells that makes up part of the defence mechanism in the adaptive immune system. Upon infection via invading bacteria and viruses, specific antibodies are produced to target the pathogens. An antibody pathogen complex is formed and this complex interacts with its antibody receptor to be phagocytised or opsonized and is then removed from the body. IgG is one of five classes of antibodies and is the most abundant antibody found in circulation that represents over 75% of serum antibodies in the body. The IgG antibody complex can interact with cells expressing its ...


Computational Modeling Of Rna-Small Molecule And Rna-Protein Interactions, Lu Chen Aug 2015

Computational Modeling Of Rna-Small Molecule And Rna-Protein Interactions, Lu Chen

UT GSBS Dissertations and Theses (Open Access)

The past decade has witnessed an era of RNA biology; despite the considerable discoveries nowadays, challenges still remain when one aims to screen RNA-interacting small molecule or RNA-interacting protein. These challenges imply an immediate need for cost-efficient while predictive computational tools capable of generating insightful hypotheses to discover novel RNA-interacting small molecule or RNA-interacting protein. Thus, we implemented novel computational models in this dissertation to predict RNA-ligand interactions (Chapter 1) and RNA-protein interactions (Chapter 2).

Targeting RNA has not garnered comparable interest as protein, and is restricted by lack of computational tools for structure-based drug design. To test the potential ...


The Antioxidant Activity And Their Major Antioxidant Compounds From Acanthopanax Senticosus And A. Koreanum, Young-Hyun Kim, Myoung Lae Cho, Dan-Bi Kim, Gi-Hae Shin, Jin-Ha Lee, Jong Seok Lee, Sun-Ok Park, Sang-Jong Lee, Hyun Mu Shin, Ok-Hwan Lee Jul 2015

The Antioxidant Activity And Their Major Antioxidant Compounds From Acanthopanax Senticosus And A. Koreanum, Young-Hyun Kim, Myoung Lae Cho, Dan-Bi Kim, Gi-Hae Shin, Jin-Ha Lee, Jong Seok Lee, Sun-Ok Park, Sang-Jong Lee, Hyun Mu Shin, Ok-Hwan Lee

Open Access Articles

The antioxidant activity and chlorogenic acid and caffeic acid contents were investigated from different parts of Acanthopanax senticosus and A. koreanum. Antioxidant activity was assessed by various in vitro assays such as DPPH, ABTS, FRAP, reducing power assays and ORAC, and the chlorogenic acid and caffeic acid were validated by HPLC chromatography. Among the various extracts, the fruit extracts of A. senticosus and A. koreanum exhibited strongest antioxidant activities including ABTS, FRAP, reducing power and ORAC, however, strongest DPPH radical scavenging activity was observed from the leaf extract of A. senticosus. In addition, the antioxidant activities of various extracts were ...


Design, Synthesis, And Pharmacological Evaluation Of Three Series Of Lobelane Analogs As Inhibitors Of The Vesicular Monoamine Transporter (Vmat2), John P. Culver Jan 2015

Design, Synthesis, And Pharmacological Evaluation Of Three Series Of Lobelane Analogs As Inhibitors Of The Vesicular Monoamine Transporter (Vmat2), John P. Culver

Theses and Dissertations--Pharmacy

Methamphetamine (METH) abuse is a serious problem in the United States and worldwide. The reward experienced by METH users is due to the increase in extracellular dopamine (DA) concentrations caused by an interaction between METH and the DA transporter (DAT) as well as the Vesicular Monoamine Transporter-2 (VMAT2). The reward felt by users of METH leads to further use of the drug and subsequent abuse. The current project examined the ability of three novel series of lobelane analogs to interact with a binding site on the Vesicular Monoamine Transporter-2 (VMAT2) in an attempt to inhibit the effects of METH. Lobelane ...


Inhibition Of The Thioesterase Activity Of Human Fatty Acid Synthase By 1,4- And 9,10-Diones, Herman H. Odens Sep 2014

Inhibition Of The Thioesterase Activity Of Human Fatty Acid Synthase By 1,4- And 9,10-Diones, Herman H. Odens

Faculty Works

Fatty acid synthase (FASN) is the enzyme that synthesizes fatty acids de novo in human cells. Although FASN is generally expressed at low levels in most normal tissues, its expression is highly upregulated in many cancers. Consistent with this notion, inhibition of FASN activity has demonstrated potential to halt proliferation and induce cell death in vitro and to block tumor growth in vivo. Consequently, FASN is widely recognized as a valuable therapeutic target. In this report, we describe a variety of 1,4-quinones and 9,10- anthraquinones, including several natural compounds and some newly synthesized compounds, that potently inhibit the ...


Design, Synthesis And Biological Evaluation Of Novel Compounds With Cns-Activity Targeting Cannabinoid And Biogenic Amine Receptors, Alexander M. Sherwood May 2014

Design, Synthesis And Biological Evaluation Of Novel Compounds With Cns-Activity Targeting Cannabinoid And Biogenic Amine Receptors, Alexander M. Sherwood

University of New Orleans Theses and Dissertations

This work seeks to contribute to the discipline of neuropharmacology by way of structure activity relationship from the standpoint of an organic chemist. More specifically, we sought to develop robust synthetic methodology able to efficiently produce an array of compounds for the purpose of systematic evaluation of their interaction with specific sights within the central nervous system (CNS) in order to better understand the mind and to develop drugs that may have beneficial effects on neurological function.

The focus of these studies has been toward the development of novel molecules, using a structure-activity relationship approach, that exhibit binding affinity at ...


Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres Jan 2014

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of ...


Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit Jan 2014

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 ...


New Applications Of Mass Spectrometry For Drug And Lipid Analysis, Elizabeth Lauren Emerson Dec 2012

New Applications Of Mass Spectrometry For Drug And Lipid Analysis, Elizabeth Lauren Emerson

Theses and Dissertations

Mass spectrometry is an important tool used in many different disciplines and settings that include forensics, drug discovery, environmental analysis, and proteomics. Gas chromatography - mass spectrometry (GC-MS) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI - TOF MS) are two of the most important instruments used for analysis of compounds. Chapters 1 and 2 of this discussion use GC-MS for the investigation of synthetic cannabinoids in `K2' incense products and the detection of metabolites in urine samples from individuals suspected of consuming these mixtures. Analytical standards were synthesized and used for identification and confirmation of structures. Detection of these ...


Structural Properties Of Thermoresponsive Poly(N-Isopropylacrylamide)-Poly(Ethyleneglycol) Microgels, J. Clara-Rahola, A. Fernandez-Nieves, B. Sierra-Martin, A. B. South, L. Andrew Lyon, J. Kohlbrecher, A. F. Barbero Jan 2012

Structural Properties Of Thermoresponsive Poly(N-Isopropylacrylamide)-Poly(Ethyleneglycol) Microgels, J. Clara-Rahola, A. Fernandez-Nieves, B. Sierra-Martin, A. B. South, L. Andrew Lyon, J. Kohlbrecher, A. F. Barbero

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The application of RNA interference to treat disease is an important yet challenging concept in modern medicine. In particular, small interfering RNA (siRNA) have shown tremendous promise in the treatment of cancer. However, siRNA show poor pharmacological properties, which presents a major hurdle for effective disease treatment especially through intravenous delivery routes. In response to these shortcomings, a variety of nanoparticle carriers have emerged, which are designed to encapsulate, protect, and transport siRNA into diseased cells. To be effective as carrier vehicles, nanoparticles must overcome a series of biological hurdles throughout the course of delivery. As a result, one promising ...


In Vivo Quantitative Study Of Sized-Dependent Transport And Toxicity Of Single Silver Nanoparticles Using Zebrafish Embryos, Kerry J. Lee, Lauren M. Browning, Prakash D. Nallathamby, Tanvi Desai, Pavan K. Cherukui, Xiao-Hong Nancy Xu Jan 2012

In Vivo Quantitative Study Of Sized-Dependent Transport And Toxicity Of Single Silver Nanoparticles Using Zebrafish Embryos, Kerry J. Lee, Lauren M. Browning, Prakash D. Nallathamby, Tanvi Desai, Pavan K. Cherukui, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Nanomaterials possess distinctive physicochemical properties (e.g., small sizes and high surface area-to-volume ratios) and promise a wide variety of applications, ranging from the design of high quality consumer products to effective disease diagnosis and therapy. These properties can lead to toxic effects, potentially hindering advances in nanotechnology. In this study, we have synthesized and characterized purified and stable (nonaggregation) silver nanoparticles (Ag NPs, 41.6 ± 9.1 nm in average diameter) and utilized early developing (cleavage-stage) zebrafish embryos (critical aquatic and eco- species) as in vivo model organisms to probe the diffusion and toxicity of Ag NPs. We found ...


Parallel Text Immersion, Daniel P. Becker Ph.D. Dec 2011

Parallel Text Immersion, Daniel P. Becker Ph.D.

Daniel P. Becker

A new method of teaching foreign languages to beginning, intermediate, and advancing foreign language students is proposed involving reading out loud passages, chapters, and entire works of literature that are familiar to the student through required pre-reading in the students’ mother tongue. Testing is proposed to evaluate the success of the method.


Liquid Chromatography-Tandem Mass Spectrometry For The Determination Of Methylprednisolone In Rat Plasma And Liver After Intravenous Administration Of Its Liver-Targeted Dextran Prodrug, Shuang-Qing Zhang, Helen R. Thorsheim, Suman Penugonda, Venkateswaran C. Pillai, Quentin R. Smith, Reza Mehvar Jan 2009

Liquid Chromatography-Tandem Mass Spectrometry For The Determination Of Methylprednisolone In Rat Plasma And Liver After Intravenous Administration Of Its Liver-Targeted Dextran Prodrug, Shuang-Qing Zhang, Helen R. Thorsheim, Suman Penugonda, Venkateswaran C. Pillai, Quentin R. Smith, Reza Mehvar

Pharmacy Faculty Articles and Research

A specific and sensitive liquid chromatography (LC)-tandem mass spectrometric method for quantitative determination of methylprednisolone (MP) in rat plasma and liver was developed and validated using triamcinolone acetonide as an internal standard. Liquid-liquid extraction using tert-butyl methyl ether was used to extract the drug and the internal standard from plasma and liver. The separation of MP was performed on a C(18) column with a mobile phase of acetonitrile:0.5% formic acid aqueous solution (85:15, v/v) over 4 min. The assay was based on the selected reaction monitoring transitions at m/z 375 -> 161 for MP ...


Synthesis Of Multifunctional Nanogels Using A Protected Macromonomer Approach, Neetu Singh, L. Andrew Lyon Jan 2008

Synthesis Of Multifunctional Nanogels Using A Protected Macromonomer Approach, Neetu Singh, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nanoparticles possessing multiple functionalities provide synthetic handles for varied surface chemistries, making them useful for a range of applications such as biotargeting and drug delivery. However, the combination of interfering functionalities on the same particle is often challenging. We have employed a synthetic scheme involving chemical protection/deprotection to combine interfering functional groups on the same hydrogel nanoparticle. The synthesis of amine-containing poly(N-isopropylacrylamide) nanogels was carried out via free radical precipitation polymerization by incorporating a Fmoc-protected amine poly(ethylene glycol) (PEG) macromonomer. The Fmoc group was then removed to obtain free amines, which were shown to be available for ...