Pharmaceutics and Drug Design Commons^™

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …

Phenylpyrazalopyrimidines As Tyrosine Kinase Inhibitors: Synthesis, Antiproliferative Activity, And Molecular Simulations, Bhupender S. Chhikara, Sajda Ashraf, Saghar Mozaffari, Nicole St. Jeans, Dindyal Mandal, Rakesh Kumar Tiwari, Zaheer Ul-Haq, Keykavous Parang

Pharmacy Faculty Articles and Research

N1-(α,β-Alkene)-substituted phenylpyrazolopyrimidine derivatives with acetyl and functionalized phenyl groups at α- and β-positions, respectively, were synthesized by the reaction of 3-phenylpyrazolopyrimidine (PhPP) with bromoacetone, followed by a chalcone reaction with differently substituted aromatic aldehydes. The Src kinase enzyme assay revealed modest inhibitory activity (half maximal inhibitory concentration, IC₅₀ = 21.7–192.1 µM) by a number of PhPP derivatives. Antiproliferative activity of the compounds was evaluated on human leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3), breast carcinoma (MDA-MB-231), and colon adenocarcinoma (HT-29) cells in vitro. 4-Chlorophenyl carbo-enyl substituted 3-phenylpyrazolopyrimidine (10) inhibited the cell proliferation of HT-29 and SK-OV-3 by 90% …

The Effects Of An Adenosine A(2a) Agonist As An Adjunctive Treatment To Alleviate Sensorimotor Gating Deficits In A Rodent Model Of Schizophrenia, Hannah Rauhuff

Undergraduate Honors Theses

The adenosine system has become a promising target for the treatment of schizophrenia due to its unique relationship with dopamine D₂ receptors. Dopamine D₂ receptors display heightened sensitivity in schizophrenia, and inhibition of these receptors has been shown to alleviate some of the psychotic symptoms of the disorder. Inhibition of adenosine A(2A) receptors has been shown to decrease dopamine D₂ receptor sensitivity, making this receptor a potential target for treatment of the disorder. This effect occurs because adenosine A(2A) receptors form a mutually inhibitory heterodimeric complex with dopamine D₂ receptors. The present study looked at the …

Characterization Of Novel Cb2 Agonist Smm-295 And Its Effects In Ischemia/Reperfusion Injury, Jeffrey D. Pressly

Theses and Dissertations (ETD)

Acute kidney injury (AKI) is a major problem clinically affecting up to two-thirds of intensive care unit patients, and results in increased hospitalization time, the risk of developing chronic kidney disease, and mortality. Hallmarks of AKI include tubular cell death and a decrease in renal perfusion which leads to decreases in renal function following injury. For 20 years the pathophysiology of AKI has been well established. However, therapies for AKI have shown minimal to no success clinically. The work here describes our efforts to further categorize the effects of CB2 activation, a possible novel therapeutic target in AKI.

There is …

Evaluation Of Potential Drug Interaction Of Analgesic In Cancer Patient Receiving Palliative Care In Dharmais Cancer Hospital, Eme Stepani Sitepu, Atika Wahyu Puspitasari, Nuriza Ulul Azmi, Lila Nilam Sari

Pharmaceutical Sciences and Research

Analgesics are mostly used in cancer patients receiving palliative care to improve the quality of life of patients. Besides analgesics, cancer patients receiving palliative care were also given other drugs in combination to overcome other symptoms of cancer, and this combination could potentially cause drug interactions. This study was aimed to analyze the potential of drug interactions with analgesics in cancer patients. The study design was cross-sectional with a retrospective method and descriptive study. The sample of this study was cancer palliative care patient’s prescription at Dharmais Cancer Hospital in the period of January – December 2017. The sample analyzed …

Anti-Proliferative Effects Of A Coumarin Benjaminin On Four Human Cancer Cell Lines, Siau Hui Mah, Soek Sin Teh, Ahmad Azri Fitri Ismail, Gwendoline Cheng Lian Ee

Pharmaceutical Sciences and Research

Cancer is a major health issue around the globe. Chemotherapy and radiation therapy are no longer the standard treatments for patients as these remedies lead to many adverse effects. Thus, the development of alternative effective drugs from lead compounds, especially natural products is necessary. This study aimed to isolate cytotoxic phytochemical constituents from a plant Calophyllum inophyllum, which has been used as traditional medicine since ancient time. The root of C. inophyllum was extracted and subjected for phytochemical constituent isolation. A coumarin, benjaminin (1) was isolated successfully from the chloroform extract and its structural elucidation was performed by spectroscopy analyses …

Ace Inhibitory Activity And Functional Group Analysis Of Solvent- Partitioned Fractions Of Eleusine Indica, Jade Celon Cometa, Liahona Faith Roldan Mancol, Anthony Nalzaro Yen, Joanne Katherine Talens Manlusoc

Pharmaceutical Sciences and Research

Eleusine indica Linn. Gaerth or Indian goose grass has been widely used as an alternative natural anti-hypertensive agent. However, the rationale behind this mechanism is still unknown. The purpose of this study is to confirm the presence of functional groups that may be responsible for its ACE inhibitory activity and its possible synergism. Each solvent-portioned fraction was analyzed by FTIR, individual ACE inhibitory activity, and combination of fractions. FTIR results of solvent- partitioned fractions revealed that O-H and C-H stretches were present in all fractions. In addition to this, C-O and C=O groups were also present in all fractions except …

Assessment Of Depression Among Older Adults Staying In Old Home Care In Klang, Malaysia, Muhammad Qamar, Nurul Zahirah, Sohail Ahmad

Pharmaceutical Sciences and Research

Mental disorders such as depression are widespread, often underdiagnosed, and usually inappropriately treated. The early recognition of factors that may promote depression with the help of depression screening aid can help to plan better care for the patient. Therefore, this study aimed to determine the depression prevalence among the older adults staying in old home care, to explore any association and differences of depression across various socio-demographic variables, and to study the predictors of depression among study subjects. A cross-sectional study was conducted with a convenience sample of 141 elderly by using the validated tool. The study instrument was divided …

An Exploration Of Electrospun Fibers Containing Drug-Cyclodextrin Inclusion Complexes, Fatimah Fatimah, Zeynep Aytac, Tamer Uyar, George Pasparakis, Gareth R. Williams

Pharmaceutical Sciences and Research

A series of new core-shell fibers were developed containing anticancer drugs (5-fluorouracil or ferulic acid) and their cyclodextrin inclusion complexes, with a gadolinium-based magnetic resonance imaging (MRI) contrast agent. These were prepared by electrospinning, a simple method for producing ultra-fine fibers through the application of a strong electrostatic force on a polymer solution. The shell of the fibers was formed from Eudragit S100, and the drugs were loaded in the core. Scanning electron microscopy images showed the formation of smooth ribbon-like fibers, with diameters ranging from 1.4 to 5.1 μm, and transmission electron microscopy reveals a transparent interface between the …

Interaction Of Thymidine With Sodium Bis(2-Ethylhexyl) Sulfosuccinate In Alcohol And Water: Studies With Uv-Vis Technique, Indu M. Paudel, Ajaya Bhattarai

Pharmaceutical Sciences and Research

The accurate measurement of thymidine absorbance in the presence of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) in ethanol and water systems at room temperature by UV-vis technique has been reported. The AOT concentrations varied from 0.0005 to 0.014 [mol/L] in ethanol whereas from 0.0002 to 0.042 [mol/L] in water. The concentration of thymidine was 0.0073 [mol/L] during UV-vis spectrum registration. The thymidine spectrum was examined in the presence of AOT concentration. Using a statistical method of non-linear regression (NLREG), thymidine binding and thymidine distribution constants were evaluated. A noticeable decrease in thymidine absorbance in the presence of AOT concentration was shown in …

Formulasi Gel Ekstrak Daun Kelor (Moringa Oleifera Lamk) Sebagai Sediaan Antiinflamasi, Nining Sugihartini, Syauqul Jannah, Tedjo Yuwono

Pharmaceutical Sciences and Research

The development of anti-inflammatory gel of Moringa oleifera leaf extract has been performed. This study aimed to determine the physical properties, irritation index and anti-inflammatory activity of gel with various concentration of Moringa oleifera leaf extract. The extract was obtained by maceration method using ethanol 70%. The extracts were formulated in a gel with a concentration of 3%, 6%, 9% by using Carbopol 940 as gelling agent. The gel was evaluated for its physical properties (viscosity, pH, spreadability, adhesivity), irritation index with rabbit test animals and anti-inflammatory activity with mice test animals based on epidermal thickness parameters. The test results …

Profil Terapi Antihipertensi Dan Antihiperlipidemia Terhadap Fungsi Ginjal Pasien Diabetes Melitus Tipe 2 Dengan Komplikasi Penyakit Ginjal Kronis Di Rsup Dr. Hasan Sadikin, Fitri Rachmaini, Lia Amalia, Cherry Rahayu

Pharmaceutical Sciences and Research

Chronic Kidney Disease (CKD) complication increases the risk of morbidity and mortality in type 2 diabetes mellitus (DMT2) patients. The presence of hypertension and dyslipidemia as comorbidity increases the risk of macrovascular and microvascular complications and further adding to the list of drugs used. Management of this comorbidity is essential to prevent cardiovascular events and minimize kidney damage. This study aimed to evaluate therapeutic profile of antihypertensive and antihyperlipidemia drugs towards kidney function in DMT2 patients with CKD complication at Dr. Hasan Sadikin Hospital. Study was done by using a prospective single cohort design with consecutive sampling technique and obtained …

Development Of Ethanolic Extract Of Pinang Masak Jambi (Areca Catechu L.) As A Modulator Of Doxorubicin Cytotoxic Effect In Breast Cancer Therapy, Fitrianingsih Fitrianingsih, Indri Maharini, Diah Tri Utami

Pharmaceutical Sciences and Research

Doxorubicin is one of the chemotherapy agents that is often used in breast cancer therapy. Phenomenon of breast cancer cell resistance to chemotherapy agents has been traced to the molecular level. The development of compounds that can overcome drug resistance chemotherapy needs to be continuously developed, especially agents with specific molecular targets, namely P-glycoprotein (Pgp), NFkB, cyclin, and cyclin-dependent kinase (CDK). Another alternative is the combination of chemotherapy agents with chemopreventive agents (co-chemotherapy) to reduce side effects and increase sensitivity of cancer cells. Doxorubicin is often used in breast cancer therapy. This study was performed to determine the effect of …

Encapsulation Of Temulawak Extract By Using Nanocrystalline Cassava And Sago Starches And Maltodextrin, Titi Candra Sunarti, Fatimah J. Pasaribu, Christina Winarti

Pharmaceutical Sciences and Research

This study was conducted to evaluate the performance of Curcuma zanthorrhiza crude extract after encapsulated in nanocrystalline starch, and to investigate the effect of the ratio of nanocrystalline starches and maltodextrin; and the effect of concentration of temulawak extract on nanocapsule characteristics, as well as encapsulation effect on the stability of antioxidant activity. Preparation of nanocrystalline starch was conducted by using lintnerization and ethanol precipitation of cassava and sago starches. Nanocrystalline starch and maltodextrin were used as matrices with the ratio varied from 25:75, 50:50, and 75:25. The mixture of temulawak extract and matrices were homogenized and spray dried. Nanocapsules …

Vaccines In Current Culture: The Hpv Vaccine Controversy, Alyssa Johnston

Senior Honors Theses

The use of vaccinations has drastically decreased mortality and morbidity rates related to infectious disease and has become an intrinsic part of modern health care. However, the fear of risks related to vaccines has been partially responsible for the decisions of many parents to delay or avoid vaccinating their children. The human papilloma virus (HPV) vaccine specifically is one of the most controversial vaccines in current culture due to reports of new onset or exacerbation of autoimmune diseases, infertility, and even death following its administration. This review synthesizes information regarding the relevance and safety of the HPV vaccine, as well …

First-In-Human Studies Of Mw01-6-189wh, A Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, And Pharmacodynamic Studies In Healthy Adult Volunteers, Linda J. Van Eldik, Lumy Sawaki, Karen Bowen, Daniel T. Laskowitz, Robert J. Noveck, Byron Hauser, Lynn Jordan, Tracy G. Spears, Huali Wu, Kevin Watt, Shruti Raja, Saktimayee M. Roy, D. Martin Watterson, Jeffrey T. Guptill

Sanders-Brown Center on Aging Faculty Publications

MW01-6-189WH (MW189) is a novel central nervous system-penetrant small-molecule drug candidate that selectively attenuates stressor-induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first-in-human, randomized, double-blind, placebo-controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug-related treatment-emergent adverse event was infusion-site reactions, likely related to drug solution acidity. No clinically concerning changes …

Coronavirus Disease 2019 (Covid-19), Matthew Dunbar

Pharmacy Student Scholarship

No abstract provided.

Characterizing The Public Sector Contribution To Drug Discovery And Development: The Role Of Government As A First Investor, Ekaterina Galkina Cleary, Matthew Jackson, Andrew Acevedo, Fred D. Ledley

CISI Publication

This research is focused on examining the role of the public sector as an early investor in biopharmaceutical discovery and development. In the United States, the National Institutes of Health (NIH) is the primary source of funding for basic biomedical research designed to elucidate fundamental mechanisms of biology, health, and disease. This research is expected to establish the scientific foundation for the discovery and development of new biopharmaceutical products. This interim report reviews the linear model of innovation underlying these expectations, and evidence for the effectiveness of this pathway. We also describe new data demonstrating that every new drug approved …

Immunogenicity In Clinical Practice And Drug Development: When Is It Significant?, Valentina Shakhnovich, Bernd Meibohm, Amy Rosenberg, Andrzej M. Kierzek, Rachel Hasenkamp, Ryan S. Funk, Craig J. Thalhauser, Piet H. Van Der Graaf, Yow Ming C. Wang, Lora Hamuro

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Tobacco/Hiv-1-Induced Myeloid Cell-Derived Extracellular Vesicles In Hiv-1 Pathogenesis, Sanjana Haque

Theses and Dissertations (ETD)

Introduction. Smoking, which is highly prevalent in people living with HIV/AIDS, has been shown to exacerbate HIV-1 replication, in part via cytochrome P450 (CYP)-induced oxidative stress. CYP enzymes metabolize cigarette smoke condensate (CSC), causing oxidative stress and cytotoxicity. Our previous studies have demonstrated that CSC and specific CSC constituents, benzo(a)pyrene and nicotine, potentially induce CYPs, resulting in higher oxidative stress and subsequent exacerbation of HIV-1 replication in monocytes and macrophages. However, the exact mechanism behind tobacco-induced, oxidative stress-mediated enhancement of HIV-1 replication is still poorly understood. Extracellular vesicles (EVs) have recently gained attention for their unique nature as intercellular messengers …