Pharmaceutics and Drug Design Commons^™

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Designing A Calibration Set In Spectral Space For Efficient Development Of An Nir Method For Tablet Analysis, Md Anik Alam

Electronic Theses and Dissertations

Designing a calibration set is the first step in developing a spectroscopic calibration method for quantitative analysis of pharmaceutical tablets. This step is critical because successful model development depends on the suitability of the calibration data. For spectroscopic-based methods, traditional concentration based techniques for designing calibration sets are prone to have redundant information while simultaneously lacking necessary information for a successful calibration model. The traditional method also follows the same design approach for different spectroscopic techniques and different formulations, thereby lacks the optimizing capability to be technique and formulation specific.

A method for designing a calibration set in the Near …

Next Generation Of Translational Long-Acting Cabotegravir, Tian Zhou

Theses & Dissertations

Recent development of long-acting antiretroviral therapeutic regimens has opened a new chapter for HIV/AIDS management. Cabotegravir (CAB), as one of the very first long-acting antiretroviral regimens, has drawn tremendous attention. However, the remaining challenges include suboptimal dosing intervals, large injection volume, injection site reactions, lack of tissue penetration, etc. As one of the pioneers in this field, our lab was successful in harnessing mononuclear phagocytes as “Trojan horses” for antiretroviral drug delivery and transportation to viral reservoirs. We proposed this targeted delivery strategy could address the limitations of current CAB formulation. To this end, we developed folic acid decorated CAB …

Novel Determinants That Influence Azole Susceptibility In Candida Glabrata And Candida Albicans, Sarah Garland Whaley

Theses and Dissertations (ETD)

Despite the scientific and medical communities’ best efforts, the incidence of fungal infections in susceptible populations continues to rise. The most common cause of these opportunistic fungal infections is Candida. In fact, Candida is the fourth most common pathogen associated with nosocomial blood stream infections. Reported mortality rates for patients with candidemia vary, but have not decreased in the past fifteen years and are reported to be as high as 50%. Candida glabrata, second only to Candida albicans among Candida infections, expresses high rates of resistance to treatment with arguably the best class of currently available antifungals - …

Rheological Studies Of Injectable Thermoresponsive Biodegradable Hydrogels And Porcine Ocular Tissues, Chandana Reddy Damera

Theses and Dissertations (ETD)

This research has evaluated the rheological properties of two types of materials which include (i) semi-synthetic polymer-based injectable hydrogels [P(NIPAAm-co-DEX-Lactate HEMA) and P(NIPAAm-co-HA-AEMA)], and (ii) biological tissues (porcine ocular tissues).

A series of thermoresponsive and biodegradable in situ hydrogel based on N-isopropyacrylamide (NIPAAm) monomer and hydrolytically degradable oligolactate Dextran-lactate-HEMA or Hyaluronic acid (HA)-AEMA macromer were investigated as encapsulation matrices (scaffolds) for DPSCs/ADSCs and assess their applicability in dental/retinal tissue engineering. The rheological properties of the hydrogels were strongly dependent on the reaction conditions and composition of the hydrogels. Both the hydrogels exhibited linear viscoelasticity, and the values of storage moludus …

Sensitivity Of Escherichia Coli Bacteria Towards Antibiotics In Patient With Diabetic Foot Ulcer, Rafika Sari, Pratiwi Apridamayanti, Indira Diah Puspita

Pharmaceutical Sciences and Research

Chronic complication of diabetes mellitus is diabetic foot ulcers. Diabetic foot ulcer can be defined as an open wound in the feet which will become infected as the result of high blood sugar levels that develops and become place of bacteria. One of the bacteria in diabetic foot ulcer is Escherichia coli. Imprecise use of antibiotics in the treatment of diabetic foot ulcers can cause antibiotic resistance to bacteria. This study aims to determine antibiotic sensitivity of Escherichia coli bacteria in diabetic foot ulcer Wagner grade III and IV. Samples of diabetic foot ulcer swab’s with Wagner grade III and …

Optimasi Aktivitas Bakteriosin Yang Dihasilkan Oleh Bakteri Lactobacillus Plantarum Dari Minuman Ce Hun Tiau, Rafika Sari, Pratiwi Apridamayanti, Melly Octaviani

Pharmaceutical Sciences and Research

Bacteriocin is a protein compound with a small molecular weight that has an antibacterial activity. Bacteriocin has been widely applied as a natural food preservative, as it effectively prevents the growth of pathogenic bacteria in foods and beverages. The aim of this research was to know the activity of bacteriocin produced by lactic acid bacteria Lactobacillus plantarum from Ce hun tiau beverages against Escherichia coli and Staphylococcus aureuswith different pH and temperature treatments. In this study, Lactobacillus plantarum bacteria isolated from Ce hun tiau beverages were characterized by Gram staining test. Bacteriocin was extracted from Lactobacillus plantarum bacteria which had …

Aktivitas Mukolitik Kombinasi Ekstrak Etanol Daun Kemangi Dan Ekstrak Etanol Daun Sirih Merah, Neng Fisheri Kurniati, Deden Winda Suwandi, Safira Yuniati

Pharmaceutical Sciences and Research

A cough is a protective physiological mechanism that is useful for removing and clearing the respiratory tract from sputum and foreign particles that can cause infection. Treatments for cough disorders using medicinal plants were conducted because medicinal plants were widely known to have less side effects than synthetic drugs. Basil leaves (Ocimum sanctum L.) and red betel leaves (Piper crocatum Ruiz and Pav) have been used traditionally to treat a cough. The purpose of this study was to determine the mucolytic activity, and the effective concentration of the combination of basil and red betel leaves ethanol extract. The mucolytic activity …

Peran Tenaga Kefarmasian Dalam Penanggulangan Bencana Role Of Pharmacist In Disaster Management, Meutia Faradilla

Pharmaceutical Sciences and Research

Indonesia is a country that has high potency to be affected by disaster, either by natural or man-made disaster. After the 2004 tsunami, Indonesian government has improved its disaster prevention policy and program. In disaster management study, health management in disaster setting is aimed to assure the implementation of health service toward victims accordingly. As integrated part of the healthcare team in disaster management, pharmacists have to understand the importance of pharmaceutical care in pre-disaster, disaster, and post-disaster phase. This article aims to provide an overview on pharmacists’ role in disaster management from preparing and distributing medicine and medical devices …

Potency Of (Poly) Acrylic/Carboxymethyl Starch-Chitosan Biohydrogel For Curcumin Oral Delivery Matrix, Eka Ruriani, Djumali Mangunwidjaja, Nur Richana, Titi Candra Sunarti

Pharmaceutical Sciences and Research

Biohydrogel has gathered great interest in the pharmaceuticals field. This natural polymers were biodegradable, non-toxic, biocompatible, and its specific ability to response environment change can be considered for the controlled released matric of bioactive compound. In this study, the biohydrogel was synthesized by graft-copolymerization of acrylic acid onto carboxymethyl starch (CMS) and chitosan. The objective of this research was to determine the effect of CMS-chitosan ratio on the biohydrogel characteristic. The acrylic acid was grafted on to the backbone (3:1) using cerric ammonium nitrate as the inisiator.A standarded curcumin was applied to test the binding potency of matrix. A higher …

Evaluation Of Propolis And Milk Administration On Caffein-Induced Mus Musculus Fetus Skeletal, Dwisari Dillasamola, Almahdy A, Novita Purnama Sari, Biomechy Oktomalio Putri, Noverial Noverial, Skunda Diliarosta

Pharmaceutical Sciences and Research

Caffeine consumption by pregnant women at doses above 300 mg/day was suggested to cause skeletal damage. Propolis with high flavonoids concentration could increase the number of osteoblasts. This research aims to evaluate the effect of propolis and milk administration on fetal skeletal of caffeine-induced female mice (Mus musculus). Mice were divided into six groups: negative group, positive group of caffeine (a dose of 75 mg/kg BW), positive group of propolis (a dose of 1400 mg/kg BW), positive group of milk (200 ml), group D1 (caffeine 75 mg/kg BW and propolis 1400 mg/kg BW) and group D2 (caffeine 75 mg/kg BW …

Evaluasi Rasionalitas Penggunaan Obat Antihipertensi Di Puskesmas Siantan Hilir Kota Pontianak Tahun 2015, Eka Kartika Untari, Alvani Renata Agilina, Ressi Susanti

Pharmaceutical Sciences and Research

Hypertension is widely known as cardiovascular disease. In addition to resulting heart failure, hypertension can result in kidney failure and cerebrovascular disease. This study was aimed to determine the percentage of treatment rationality of hypertensive patient treatment outpatient in Puskesmas Siantan Hilir Pontianak 2015 which includes the appropriate indication, appropriate drug, appropriate patient, and appropriate dose based on the guideline JNC 7. This study was cross-sectional study using medical records of outpatient hypertension patients in 2015. The total of sample analyzed in this research were 92 medical records of hypertension patients from 118 medical records. The percentage of using the …

Discovery And Effects Of Pharmacological Inhibition Of The E3 Ligase Skp2 By Small Molecule Protein-Protein Interaction Disruptors, John K. Morrow

Dissertations and Theses (Open Access)

Skp2 (S-phase kinase-associated protein 2), one component of the SCF E3 ubiquitin ligase complex, directly interacts with Skp1 and indirectly associates with Cullin1 and Rbx1 to bridge the E2 conjugating enzyme with its protein substrate to execute its E3 ligase activity. Skp2 is an Fbox protein (due to it containing an Fbox domain) and it is the rate-limiting component of the SCF complex. Skp2 targets several cell-cycle regulatory proteins for ubiquitination and degradation; most notable and significant for cancer are the cyclin-dependent kinase inhibitor, p27. Skp2 is an oncogene and studies have shown that over-expression of Skp2 leads to increased …

Microscopic Allies: Examining And Tackling Legal And Regulatory Barriers To The Development Of Phage Therapy, Jacob Zent

William & Mary Environmental Law and Policy Review

No abstract provided.

Synthesis, Characterization, And In Vitro Cytotoxicity Of Fatty Acyl-Cgkrk-Chitosan Oligosaccharides Conjugates For Sirna Delivery, Naglaa Salem El-Sayed, Meenakshi Sharma, Hamidreza Montazeri Aliabadi, Magda Goda El-Meligy, Ahmed Kamed El-Zaity, Zenat Adeeb Nageib, Rakesh Tiwari

Pharmacy Faculty Articles and Research

In this studies, three fatty acyl derivatives of CGKRK homing peptides were coupled successfully to chitosan oligosaccharides (COS) using sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate sodium salt (sulfo-SMCC). The COS-SMCC was prepared by direct coupling between COS and sulfo-SMCC in PBS (pH 7.5) at RT for 48 h. The structure of COS-SMCC and the three fatty acyl-CGKRK-SMCC-COS conjugates were characterized by FT-IR, ¹³C NMR, and SEM. The ability of three conjugates to condense siRNA into nanosized polyplexes and their efficacy in protecting siRNA from serum nucleases degradation were investigated. Among the investigated derivatives, S-CGKRK-COS showed higher siRNA binding affinity as compared to …

Cost-Effectiveness Analysis Of Metformin+Dipeptidyl Peptidase-4 Inhibitors Compared To Metformin+Sulfonylureas For Treatment Of Type 2 Diabetes, Christina S. Kwon, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

Background: Patients with type 2 diabetes (T2D) typically use several drug treatments during their lifetime. There is a debate about the best second-line therapy after metformin monotherapy failure due to the increasing number of available antidiabetic drugs and the lack of comparative clinical trials of secondary treatment regimens. While prior research compared the cost-effectiveness of two alternative drugs, the literature assessing T2D treatment pathways is scarce. The purpose of this study was to evaluate the long-term cost-effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) as second-line therapy in combination with metformin in patients with T2D.

Methods: …

Amine Containing Analogs Of Sulindac For Cancer Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

Pharmaceutical Sciences Faculty Publications

Background:

Sulindac belongs to the chemically diverse family of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that effectively prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA), an amide analog of sulindac sulfide, shows insignificant COX-related activity and toxicity while enhancing anticancer activity in vitro and demonstrating in vivo xenograft activity.

Objective:

Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities.

Method:

A series of sulindac amine analogs were designed and synthesized and then further modified in a “libraries from libraries” approach to produce amide, sulfonamide and N,N-disubstituted …

Detection And Quantification Of Glucuronidation Of Ursolic Acid (Ua) In Human Liver Microsomes (Hlms)., Kamola Tolliboeva, Philip M. Gerk

UROP Posters

No abstract provided.

The Morality Of Compulsory Licensing As An Access To Medicines Tool, Margo A. Bagley

Faculty Articles

This Article contemplates the validity of theft rhetoric in relation to the right of countries to grant compulsory licenses from an unconventional perspective; that of biblical teachings on what it means to steal.

Part I describes the use of theft rhetoric in relation to IP infringement broadly and drug-patent compulsory licenses in particular.

Part II challenges the contention, suggested by theft rhetoric, that compulsory licenses are morally wrong as a form of stealing, by considering the meaning of theft in the context of its Judeo-Christian origins.

Part III considers the cogency of the accusation that the issuance of compulsory licenses …

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 …

Discovery Of New Antimicrobial Options And Evaluation Of Aminoglycoside Resistance Enzyme-Associated Resistance Epidemic, Selina Y. L. Holbrook

Theses and Dissertations--Pharmacy

The extensive and sometimes incorrect and noncompliant use of various types of antimicrobial agents has accelerated the development of antimicrobial resistance (AMR). In fact, AMR has become one of the greatest global threat to human health in this era. The broad-spectrum antibiotics aminoglycosides (AGs) display excellent potency against most Gram-negative bacteria, mycobacteria, and some Gram-positive bacteria, such as Staphylococcus aureus. The AG antibiotics amikacin, gentamicin, kanamycin, and tobramycin are still commonly prescribed in the U.S.A. for the treatment of serious infections. Unfortunately, bacteria evolve to acquire resistance to AGs via four different mechanisms: i) changing in membrane permeability to …

Development And Preclinical Evaluation Of Long-Lasting Cocaine Hydrolases For Cocaine Overdose And Cocaine Use Disorder Treatment, Ting Zhang

Theses and Dissertations--Pharmacy

Cocaine is a plant-based illicit drug commonly involved in substance use disorder. Although cocaine overdose and cocaine use disorders cause adverse health consequences to individuals and the economic burden on their family and society, there are no FDA (Food and Drug Administration) approved medications for treatment. Recently, it has been recognized that delivery of cocaine hydrolase (CocH) is a promising therapeutic strategy. Human butyrylcholinesterase (hBChE), the primary enzyme involved in cocaine metabolism in human, have advantages over other candidates for the development of CocH. Previous studies in our laboratory have designed and characterized hBChE mutants that have ~4,000-fold improved catalytic …

Using The Qbest Equation To Evaluate Ellagic Acid Safety Data: Generating A Qnoael With Confidence Levels From Disparate Literature, Cynthia Rose Dickerson

Theses and Dissertations--Pharmacy

QBEST, a novel statistical method, can be applied to the problem of estimating the No Observed Adverse Effect Level (NOAEL or QNOAEL) of a New Molecular Entity (NME) in order to anticipate a safe starting dose for beginning clinical trials. The NOAEL from QBEST (called the QNOAEL) can be calculated using multiple disparate studies in the literature and/or from the lab. The QNOAEL is similar in some ways to the Benchmark Dose Method (BMD) used widely in toxicological research, but is superior to the BMD in some ways. The QNOAEL simulation generates an intuitive curve that is comparable to the …

Scalable Feature Selection And Extraction With Applications In Kinase Polypharmacology, Derek Jones

Theses and Dissertations--Computer Science

In order to reduce the time associated with and the costs of drug discovery, machine learning is being used to automate much of the work in this process. However the size and complex nature of molecular data makes the application of machine learning especially challenging. Much work must go into the process of engineering features that are then used to train machine learning models, costing considerable amounts of time and requiring the knowledge of domain experts to be most effective. The purpose of this work is to demonstrate data driven approaches to perform the feature selection and extraction steps in …

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 …

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 …

Evaluation Of A Drug Delivery System Based On Cyclodextrins For Cancer Therapy, Caroline Mendes

Doctoral

Due to the side-effects caused by regular chemotherapy, the development of drug delivery systems that can specifically target cancer cells and deliver the therapeutic dose is required. In this study, a folate-derivative of β-cyclodextrin has been studied as a vehicle for targeting folate receptors (FR) and delivering the chemotherapeutic drug methotrexate (MTX). FRs can be considered key cell membrane targets since they are commonly over-expressed in cancer cells and play an important role in cancer development and progression. Cyclodextrins (CDs) are cyclic oligosaccharides with a unique structure that allows them to form inclusion complexes with guest molecules, increasing their aqueous …

Discovery Of Natural Product Analogs Against Ethanol-Induced Cytotoxicity In Hippocampal Slice Cultures, Meredith A. Saunders-Mattingly

Theses and Dissertations--Psychology

An estimated 13.9% of Americans currently meet criteria for an alcohol (ethanol; EtOH) use disorder (AUD). While there are 4 medications approved by the Food and Drug Administration (FDA) to treat AUD, these treatments have demonstrated poor clinical efficacy. Our ongoing research program encompasses a multi-tiered screening of a natural product library and validation process to provide novel information about the mechanisms underlying EtOH-induced changes in neurobiology and to identify novel chemical scaffolds to be exploited in the development of pharmacological treatments for AUD in a rodent organotypic hippocampal slice culture model. Initial screens of several natural product compounds identified …

Elucidation Of Substrate Binding Interactions For Human Organic Cation Transporters 1 (Slc22a1) And 2 (Slc22a2) Using In Silico Homology Modeling In Conjunction With In Vitro Site-Directed Mutagenesis And Kinetic Analysis, Raymond E. Lai

Theses and Dissertations

The organic cation transporters (OCTs) play a critical role in the absorption, distribution and elimination of many drugs, hormones, herbal medicines, and environmental toxins. Given the broad substrate specificity of OCTs, they fall victim to the high susceptibility for contributing to harmful drug-drug interactions. Further defining how human (h)OCTs mechanistically bind to its broad array of substrates will provide significant insight to the understanding and prediction of drug-drug interactions in polypharmacy patients and the advancement of future rational drug design for therapeutics targeting OCTs. The goal of the current study was to elucidate the critical amino acid residues for transporter-substrate …