Pharmaceutics and Drug Design Commons^™

Development Of A Multivalent Subunit Vaccine Against Tularemia Using Tobacco Mosaic Virus (Tmv) Based Delivery System, Sukalyani Banik, Ahd Ahmed Mansour, Ragavan Varadharajan Suresh, Sherri Wykoff-Clary, Meenakshi Malik, Alison A. Mccormick, Chandra Shekhar Bakshi

Faculty Publications & Research of the TUC College of Pharmacy

Francisella tularensisis a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV) based delivery platform. The multivalent subunit vaccine was formulated …

In Planta Production Of Flock House Virus Transencapsidated Rna And Its Potential Use As A Vaccine, Yiyang Zhou, Payal D. Maharaj, Jyothi K. Mallajosyula, Alison A. Mccormick, Christopher M. Kearney

Faculty Publications & Research of the TUC College of Pharmacy

We have developed a transencapsidated vaccine delivery system based on the insect virus, Flock House virus (FHV). FHV is attractive due to its small genome size, simple organization, and non-pathogenic characteristics. With the insertion of a Tobacco mosaic virus (TMV) origin of assembly (Oa), the independently replicating FHV RNA1 can be transencapsidated by TMV coat protein. In this study we demonstrated that the Oa adapted FHV RNA1 transencapsidation process can take place in planta, by using a bipartite plant expression vector system, where TMV coat protein is expressed by another plant virus vector, Foxtail mosaic virus (FoMV). Dual infection in …

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Kinetics And Mechanisms Of Crystal Growth Inhibition Of Indomethacin By Model Precipitation Inhibitors, Dhaval D. Patel

Theses and Dissertations--Pharmacy

Supersaturating Drug Delivery Systems (SDDS) could enhance oral bioavailability of poorly water soluble drugs (PWSD). Precipitation inhibitors (PIs) in SDDS could maintain supersaturation by inhibiting nucleation, crystal growth, or both. The mechanisms by which these effects are realized are generally unknown. The goal of this dissertation was to explore the mechanisms underpinning the effects of model PIs including hydroxypropyl β-cyclodextrins (HP-β-CD), hydroxypropyl methylcellulose (HPMC), and polyvinylpyrrolidone (PVP) on the crystal growth of indomethacin, a model PWSD. At high degrees of supersaturation (S), the crystal growth kinetics of indomethacin was bulk diffusion-controlled, which was attributed to a high energy form deposited …

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

A Molecular-Level View Of The Physical Stability Of Amorphous Solid Dispersions, Xiaoda Yuan

Theses and Dissertations--Pharmacy

Many pharmaceutical compounds being developed in recent years are poorly soluble in water. This has led to insufficient oral bioavailability of many compounds in vitro. The amorphous formulation is one of the promising techniques to increase the oral bioavailability of these poorly water-soluble compounds. However, an amorphous drug substance is inherently unstable because it is a high energy form. In order to increase the physical stability, the amorphous drug is often formulated with a suitable polymer to form an amorphous solid dispersion. Previous research has suggested that the formation of an intimately mixed drug-polymer mixture contributes to the stabilization …

Elaboration And Design Of Α7 Nachr Negative Allosteric Modulators, Osama I. Alwassil

Theses and Dissertations

α7 Neuronal nicotinic acetylcholine receptors are one of two major classes of receptors responsible for cholinergic neurotransmission in the central nervous system. The existence of α7 neuronal nAChRs in different regions of the nervous system suggests their involvement in certain essential physiological functions as well as in disorders such as Alzheimer’s disease (AD), drug dependence, and depression. This project was aimed toward the discovery and development of small–molecule arylguanidines that modulate α7 nAChR function with improved subtype-selectivity through an allosteric approach. Identifying the required structural features of these small molecules allowed optimization of their negative allosteric modulator (NAM) actions at …

Feasibility Of Integrating Tripterygium Wilfordii Into Modern Cancer Therapy For Increased Efficacy And Minimal Toxicity, Ngoc T. Vo

UROP Posters

Cancer is the second leading cause of death in the U.S. and millions of novel cancer cases are being diagnosed each year. While chemotherapy and ionizing radiation are effective treatments against these malignant tumors, the adverse effects that accompany such treatments are devastating. In order to find alternative treatment methods with less side effects, we turn to Eastern herbal medicine. Recent scientific research has found that Tripterygium wilfordii, an herbal medicine traditionally used to treat inflammation in China, contains compounds (triptolide and celastrol) that prevent the growth of solid tumors, induce apoptosis, and prevent metastasis of developed tumors. Investigations …

Investigation Of Phenylephrine Sulfation And Inhibition Using A Novel Hilic Assay Method, Heta N. Shah

Theses and Dissertations

Phenylephrine (PE) is the most commonly used over-the-counter nasal decongestant. The problem associated with phenylephrine is that it undergoes extensive first pass metabolism in the intestinal gut wall leading to its poor and variable oral bioavailability.

This research project aims at developing strategies in order to increase the oral bioavailability of PE by co-administration of GRAS compounds. A HILIC assay method was developed to detect the parent drug, phenylephrine (PE) and its sulfate metabolite (PES).The enzyme kinetic studies were done with phenolic dietary or GRAS compounds using LS180 human intestinal cell model, recombinant SULT enzymes and human intestinal cytosol (HIC). …

Efek Fraksi N-Heksana Kulit Hylocereus Polyhizus Terhadap Kadar Malondialdehida Tikus Stres Oksidatif, Wirna Maya Sari, Sri Wahdaningsih, Eka Kartika Untari

Pharmaceutical Sciences and Research

Excessive free radical production will lead to oxidative stress. One of the indicators used to determine stress oxidative is malondialdehyde (MDA). Hylocereus polyhizus peel is potential used natural exogenous antioxidant. The aim of this research was to study the effect of n-hexane fraction of H.polyhizus peel on MDA level and to determine the dose that could reduce the MDA level. H.polyhizus peel was macerated with chloroform, fractionated with n-Hexane. Rats were divided into 7 groups : normal, negative, positive control vitamin E (18 mg/ kgbw), positive control quercetin (4 mg/200gbw), H.polyhizus peel extract group treated with dose I (10mg/ 200gbw), …

Efek Fraksi N-Heksana Kulit Hylocereus Polyrhizus Terhadapaktivitas Katalase Tikus Stres Oksidatif, Eka Kartika Untari, Sri Wahdaningsih, Agustia Damayanti

Pharmaceutical Sciences and Research

Production of excess free radicals cause oxidative damage and degenerative diseases. Catalase enzyme is one of the endogenous intracellular antioxidant that can be reduced by oxidative stress conditions. The peel of red dragon fruit (Hylocereus polyrhizus) as a potent exogenous antioxidants could support the internal enzyme activity to prevent free radicals. The aim of this research was to determine the effect of n-hexane fraction of H.polyrhizus’s peel and the dose that could increase activity of catalase. The peel was maserated with chloroform, then fractionated by n-hexane. Stress condition was achieved by five days fasting and swimming for 10 mins/day to …

Formulasi Krim Antioksidan Ekstrak Etanol Daun Ubi Jalar Ungu (Ipomoea Batatas (L.) Lamk) Sebagai Anti Aging, Damaranie Dipahayu, Widji Soeratri, Mangestuti Agil

Pharmaceutical Sciences and Research

No abstract provided.

Antibakteri Fraksi N-Heksana Kulit Hylocereus Polyrhizus Terhadap Staphylococcus Epidermidis Dan Propionibacterium Acnes, Sri Wahdaningsih, Eka Kartika Untari, Yunita Fauziah

Pharmaceutical Sciences and Research

Acne can be caused by Staphylococcus epidermidis and Propionibacterium acnes. By using antibiotic for the acne theraphy in a long term period can cause resistance, organ detriment and imunohypersensitivity. Red dragon fruit’s peel (Hylocereus polyrhizus) is one of natural materials which can be used for alternative antibacterial. This study aims to determine the antibacterial activity of n-Hexane fraction of red dragon fruit’s peel against S. epidermidis dan P. acnes by the method of disc diffusion Kirby-Bauer. Red dragon fruit’s peel powder macerated within chloroform, and macerate then fractionated with n-Hexane. Phytochemical screening result red dragon fruit’s peel contains terpenoid and …

Uji Stabilitas Fisik Formula Krim Yang Mengandung Ekstrak Kacang Kedelai (Glycine Max), Rosmala Dewi, Effionora Anwar, Yunita Ks

Pharmaceutical Sciences and Research

Soybean extract has known for its antiaging potential. The addition of soybean extract was predicted can influence the physical stability of the cream. Therefore, this research was aimed to test the physical stability of cream contained soybean extract in different concentration (2%, 4%, 6%, and 8%). The physical stability test including the storage for eight weeks at room temperature, high temperature (40°±2°C), and low temperature (4°±2°C). Stability parameters were the organoleptic observation, pH, globul size, viscosity, and cycling test. Those four cream formula showed good stability in organoleptic, pH, globul size, viscosity, and cycling test.

Computer-Aided Drug Design And Discovery, Screening And Synthesis Of Small Molecule Inhibitors Of Nucleoside Transporters, Hilaire Colleen Playa

Theses and Dissertations (ETD)

Using prior biological data, pharmacophore models were made for hCNT1, hCNT3, hENT1, and hENT4. The hCNT3 and hCNT1 pharmacophore were used to select compounds for biological testing. The NBMPR analogue and dipyridamole analogue hENT1 pharmacophores were compared to each other and to a combined pharmacophore for hENT1. The dipyridamole analogue pharmacophore better predicted non-nucleoside small molecule inhibitors, and as such appears to be the better tool for aiding in the design of new small molecule inhibitors. The hCNT3 pharmacophore failed to select active compounds and as such must be redesigned. The hCNT1 pharmacophore succeeded in identifying two moderately active compounds …

Nucleoside Reverse Transcriptase Inhibitors Possess Intrinsic Anti-Inflammatory Activity, Benjamin J. Fowler, Bradley D. Gelfand, Younghee Kim, Nagaraj Kerur, Valeria Tarallo, Yoshio Hirano, Shoba Amarnath, Daniel H. Fowler, Marta Radwan, Mark T. Young, Keir Pittman, Paul Kubes, Hitesh Agarwal, Keykavous Parang, David R. Hinton, Ana Bastos-Carvalho, Shengjian Li, Testuhiro Yasuma, Takeshi Mizutani, Reo Yasuma, Charles Wright, Jayakrishna Ambati

Pharmacy Faculty Articles and Research

Nucleoside reverse transcriptase inhibitors (NRTIs) are mainstay therapeutics for HIV that block retrovirus replication. Alu (an endogenous retroelement that also requires reverse transcriptase for its life cycle)–derived RNAs activate P2X7 and the NLRP3 inflammasome to cause cell death of the retinal pigment epithelium in geographic atrophy, a type of age-related macular degeneration. We found that NRTIs inhibit P2X7-mediated NLRP3 inflammasome activation independent of reverse transcriptase inhibition. Multiple approved and clinically relevant NRTIs prevented caspase-1 activation, the effector of the NLRP3 inflammasome, induced by Alu RNA. NRTIs were efficacious in mouse models of geographic atrophy, choroidal neovascularization, graft-versus-host disease, and sterile …

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 thioesterase (TE) …

Uji Aktivitas Antioksidan Ekstrak Metanol Bunga Dan Daun Patikala (Etlingera Elatior (Jack) R.M.Sm) Menggunakan Metode Dpph, Virsa Handayani, Aktsar Roskiana Ahmad, Miswati Sudir

Pharmaceutical Sciences and Research

Patikala (Etlingera elatior (Jack) R.M.Sm) is a plant of the Zingiberaceae family. Patikala (E. elatior (Jack) R.M.Sm) have bioactive compounds are flavonoids that act as antioxidants. The purpose of this study was to measure free radical activity in the methanol extract of the fruit and leaves Patikala (E. elatior (Jack) R.M.Sm). Extraction of flowers and leaf samples by maceration method using methanol. Qualitative analysis of chemical compounds with certain eluent using Thin Layer Chromatography (TLC) to determine the group of active compounds in the extract. Antioxidant activity assay using the immersion method of DPPH (1,1-Diphenyl-2-picryl Hidrazil) measured absorption at a …

Potensi Pemanfaatan Nigella Sativa L. Sebagaiimunomodulator Dan Antiinflamasi, Farida Sulistiawati, Maksum Radji

Pharmaceutical Sciences and Research

Nigella sativa L. has long been used as an herbal medicine in some countries, particularly in the Middle East and in other Asian countries, including in Indonesia. One component is a protein compound extracted from black cumin oil residues, known to have efficacy to enhance the immune system and as an anti-inflammatory. As the compound will be degraded when administered orally, the research on its delivery systems, is interesting to be developed. This article will review about the prospects of their utilization and strategy formulation that preparation can be delivered orally.

Uji Efek Antiinflamasi Fraksi Air Daun Mahkota Dewa (Phaleria Macrocarpa (Shecff.) Boerl.) Terhadap Tikus Putih (Rattus Norvegicus L.), Aprilita Rina Yanti Eff, Ema Dewanti, Melisha Adelina H

Pharmaceutical Sciences and Research

Inflammation occurs as the attempt of body to inactivate organisms that attack the body, removing irritants and regulate tissue repair. One of the medicinal plants used empirically as antiinflammation is the leaf of Mahkota Dewa (Phaleria macrocarpa (Schecff.) Boerl). This study investigated the effect of anti-inflammatory water fraction of leaf Mahkota Dewa using oedema induction method with caragenin in rat. Water fraction of Mahkota Dewa was given at the dose 0.5 g/kg BW ,1 g/kg BW and 2 g/kg BW. Sodium diclofenac was used as a positive control and CMC as negative control. The result showed water fractions of three …

Efek Ekstrak Etanol Daun Premna Cordifolia Terhadap Malondialdehida Tikus Yang Dipapar Asap Rokok, Asri Adyttia, Eka Kartika Untari, Sri Wahdaningsih

Pharmaceutical Sciences and Research

Free radical from cigarrete smoke cause lipid peroxidation that could be identified by increasing levels of Malondialdehida (MDA). Premna cordifolia leaves known having antioxidant activity in in vitro study. This study aimed to know the effect of P. cordifolia leaves extract on the levels of MDA after exposure to cigarette smoke. The simplicia extracted by maseration using 70% ethanol. Twenty four male wistar rats were divided into six groups, i.e. : control normal, negative control, positive control received cigarette smoke exposure and vitamin E (18mg/kg BW) and three groups received cigarette smoke exposure and P. cordifolia leaves extract with doses …

Tablet Effervescent Ekstrak Belimbing Wuluh (Averrhoa Bilimbi L.) Dengan Variasi Kadar Pemanis Aspartam, Rosmala Dewi, Iskandarsyah Iskandarsyah, Devi Octarina

Pharmaceutical Sciences and Research

Averrhoa bilimbi is fruit that has many benefits but the usage is not optimal. That is why the aim of the research is to get formulation of effervescent granule and tablet containing dry Averrhoa bilimbi extract with modified concentration of aspartame as sweetening agent for commercial healthy drink. Granules and tablets were produced with dry method granulation with 40% of relative humidity (RH) and 25ºC of temperature. The three of formulation were qualified as effervescent granules and tablets. Favorite tests showed that no significant differences of appearances, tastes for three of effervescent granules and tablets.

Aktivitas Penghentian Pendarahan Luar Ekstrak Etanol Daun Berenuk (Crescentia Cujete L) Secara In-Vivo, Anjar Mahardian Kusuma, Adri Nurrakhmat Sulistyo, Susanti Susanti, Sabikis Sabikis

Pharmaceutical Sciences and Research

Crescenti cujete L. or better known as calabash is a plant that thrives in Indonesia. Calabash has a great potential as an herbal remedy, but there is only some scientific research conducted on this plant, one of which is antibacterial against Bacillus subtilis and Escerichia coli on 2006 by Susanti. The method in this research was an experimental activities of the cessation external bleeding with 3 dose variation of calabash leaf extract 80%, 60%, and 40% by counting the bleeding time at base of the tail in mice. As a result, all groups of external bleeding cessation activities have better …

Effect Of Twin Screw Granulator Process Parameters On Granule Attributes, Haosheng Xu, Ridade Sayin, James Litster

The Summer Undergraduate Research Fellowship (SURF) Symposium

Twin screw wet granulation has been considered as an efficient and effective technique of manufacturing granules (agglomerates made up of small particles) and has been widely applied in pharmaceutical industry. However, narrow granule size distributions are difficult to achieve. This study aims to elucidate the effect of process parameters such as liquid feed rate and screw configuration on the granule attributes through granule characterization. The methods used are sieve analysis (for size distribution), liquid distribution (determining the dye concentration in the granules) and density and porosity (percentage gas volume in the granule) analyses. A sieve shaker is used to divide …

Electrochemical Investigations Of Benzanthrone, Antonio Trevino, Kefa Karimu Onchoke

Undergraduate Research Conference

No abstract provided.

In Vitro Metabolic Stability Study Of New Cyclen Based Antimalarial Drug Leads Using Rp-Hplc And Lc-Ms/Ms, Apoorva V. Rudraraju, Mohammad F. Hossain, Anjuli Shrestha, Prince N.A. Amoyaw, Babu L. Tekwani, M. O. Faruk Khan

Pharmaceutical Science and Research

Metabolic stability of the new antimalarial drug leads is determined using Human Liver Microsome (HLM) and specific cytochrome P450 enzyme (CYP2C8) taking the clinically used antimalarial drug chloroquine as a positive control. Experiment is done using standard methods. All the assays were conducted in 0.5 M phosphate buffer at pH 7.4. In general the metabolic reaction was initiated by adding 1 mM NADPH and 0.5 mg of enzyme. Incubations were done with time frequency of 0 hr, 1 hr, and 2 hrs at 37°C and the reactions were terminated by adding acetonitrile in the equal amounts of the assay mixture …

Hydrodynamic Cfd Modeling Of A Pharmaceutical Reactor Vessel Provided With A Retreat-Blade Impeller Under Different Baffling Conditions, Christopher G. Foehner

Theses

In the pharmaceutical industry, glass-lined reactors and vessels are often utilized to carry out a variety of different unit operations. Within these systems, both the vessel and impellers are typically glass-lined in order to provide superior corrosion resistance, prevent product contamination, and enhance cleanability. This approach, in turn, often requires the use of different, and sometimes sub-optimal, baffling conditions, which affect the hydrodynamics of the vessels and the reactor performance.

Computational Fluid Dynamics (CFD) is a computational tool that employs numerical methods and algorithms to discretize and numerically solve partial differential equations (PDEs) representing mass, energy, and momentum conservation equations …

Assessment Of A Marine Polysaccharide For Use As Excipient In Pharmaceutical Hot-Melt Extrusion, Qing Ye

Theses

Pharmaceutical Hot Melt Extrusion (HME) is currently investigated by both industry and academia as a method for manufacturing solid oral dosages with improved bioavailability of poorly-water soluble active pharmaceutical ingredients (APIs) and control drug release of water-soluble APIs. Although HME is traditionally utilizing synthetic polymers to produce such dosages, biopolymers constantly gain ground by virtue of renewability, biocompatibility and in some cases biodegradability. In this work, the possibility of using Keltone, a marine polysaccharide derived from brown seaweed, as a polymeric excipient for pharmaceutical HME is explored. Keltone is insoluble in acidic pH and soluble in basic pH, therefore making …

Dispersion And Dissolution Kinetics Of Api Particles In Pharmaceutical Hot Melt Extrusion, Wang Zhan

Theses

Pharmaceutical Hot Melt Extrusion (HME) is essentially a special case of polymer compounding. The elementary steps involved in traditional plastics melt processing are handling of particulates, melting, dispersive and distributive mixing, devolatilization and stripping, and finally pressurization and pumping. However, for pharmaceutical HME, the dissolution of the API (Active Pharmaceutical Ingredient) is an additional and very important elementary step, along with the melting of the polymeric excipient that precedes it, and mixing which accelerates the dissolution process. A major concern in pharmaceutical HME is the thermal degradation of the API. To avoid overexposure of API to heat while ensuring complete …

Experimental Determination Of The Mixing Requirements For Solid Suspension In Pharmaceutical Stirred Tank Reactors, Anqi Zhou

Theses

Glass and glass-lined, stirred-tank reactors are of significant importance in the pharmaceutical and related industries. Because of fabrication issues, a retreat blade impeller (RBI) with a low impeller clearance off the tank bottom is commonly used in glass-lined reactors, typically combined with a single baffle (providing only partial baffling conditions) mounted from the top of the reactor. In addition, these reactors are often provided with a torispherical bottom. Other configurations are also used, including full baffling or no baffles at all, hemispherical bottoms, and different impeller types. Despite their common use, some of the most important mixing characteristics of this …