Pharmaceutics and Drug Design Commons^™

Downregulation Of Mmp1 Expression Mediates The Anti-Aging Activity Of Citrus Sinensis Peel Extract Nanoformulation In Uv Induced Photoaging In Mice, Maha Salama, October University For Modern Sciences & Arts, The British University In Egypt

Pharmacy

Aging of the skin is a complicated bioprocess that is affected by constant exposure to ultraviolet irradiation. The application of herbal-based anti-aging creams is still the best choice for treatment. In the present study, Citrus sinensis L. fruit peels ethanolic extract (CSPE) was formulated into lipid nanoparticles (LNPs) anti-aging cream. Eight different formulations of CSEP-LNPs were prepared and optimized using 23 full factorial designs. In vivo antiaging effect of the best formula was tested in Swiss albino mice where photo-aging was induced by exposure to UV radiation. HPLC-QToF-MS/MS metabolic profiling of CSPE led to the identification of twenty-nine metabolites. CSPE …

Drug-Drug Interactions In Subjects Enrolled In Swog Trials Of Oral Chemotherapy, Lauren A. Marcath, Colin M. Finley, Siu Fun Wong, Daniel L. Hertz

Pharmacy Faculty Articles and Research

Background

Patients with cancer are at increased risk of drug-drug interactions (DDI), which can increase treatment toxicity or decrease efficacy. It is especially important to thoroughly screen DDI in oncology clinical trial subjects to ensure trial subject safety and data accuracy. This study determined the prevalence of potential DDI involving oral anti-cancer trial agents in subjects enrolled in two SWOG clinical trials.

Methods

Completed SWOG clinical trials of commercially available agents with possible DDI that had complete concomitant medication information available at enrollment were included. Screening for DDI was conducted through three methods: protocol-guided screening, Lexicomp® screening, and pharmacist determination …

Downregulation Of Mmp1 Expression Mediates The Anti-Aging Activity Of Citrus Sinensis Peel Extract Nanoformulation In Uv Induced Photoaging In Mice, Dalia Attia, Reham Amer, Shahira Ezzat, Nora Aborehab, Mai Ragab, Dalia Mohamed, Amira Hashad, Maha Salama, Mahitab El Bishbishy

Pharmacy

Aging of the skin is a complicated bioprocess that is affected by constant exposure to ultraviolet irradiation. The application of herbal-based anti-aging creams is still the best choice for treatment. In the present study, Citrus sinensis L. fruit peels ethanolic extract (CSPE) was formulated into lipid nanoparticles (LNPs) anti-aging cream. Eight different formulations of CSEP-LNPs were prepared and optimized using 23 full factorial designs. In vivo antiaging effect of the best formula was tested in Swiss albino mice where photo-aging was induced by exposure to UV radiation. HPLC-QToF-MS/MS metabolic profiling of CSPE led to the identification of twenty-nine metabolites. CSPE …

Mapping Km Methods And Tools Across The Pharmaceutical Product Lifecycle, Martin Lipa, Paige Kane

Level 3

Knowledge management is positioned as an enabler of ICH Q10, and the visibility and availability of product and process knowledge across the entire pharmaceutical product lifecycle is vital to the sustained success of an organization and to the effectiveness of an organization’s pharmaceutical quality system as defined by ICH Q10. This paper illustrates where knowledge management has a role to play within each product lifecycle phase. This paper goes on to further define phase-appropriate KM methods and tools to help address these needs and create end-to-end product and process knowledge visibility and availability.

Label‑Free Spectral Imaging To Study Drug Distribution And Metabolism In Single Living Cells, Qamar Alshammari, Rajasekharreddy Pala, Nir Katzir, Surya M. Nauli

Pharmacy Faculty Articles and Research

During drug development, evaluation of drug and its metabolite is an essential process to understand drug activity, stability, toxicity and distribution. Liquid chromatography (LC) coupled with mass spectrometry (MS) has become the standard analytical tool for screening and identifying drug metabolites. Unlike LC/MS approach requiring liquifying the biological samples, we showed that spectral imaging (or spectral microscopy) could provide high-resolution images of doxorubicin (dox) and its metabolite doxorubicinol (dox’ol) in single living cells. Using this new method, we performed measurements without destroying the biological samples. We calculated the rate constant of dox translocating from extracellular moiety into the cell and …

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

Comparing Long-Term Value Creation After Biotech And Non-Biotech Ipos, 1997–2016, Ekaterina Galkina Cleary, Laura M. Mcnamee, Skyler De Boer, Jeremy Holden, Liam Fitzgerald, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

We compared the financial performance of 319 BIOTECH companies focused on developing therapeutics with IPOs from 1997–2016, to that of paired, non-biotech CONTROL companies with concurrent IPO dates. BIOTECH companies had a distinctly different financial structure with high R&D expense, little revenue, and negative profits (losses), but a similar duration of listing on public markets and frequency of acquisitions. Through 2016, BIOTECH and CONTROL companies had equivalent growth in market cap and shareholder value (> $100 billion), but BIOTECH companies had lower net value creation ($93 billion vs $411 billion). Both cohorts exhibited a high-risk/high reward pattern of return, with …

Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi

Pharmaceutical Sciences (MS) Theses

Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.

The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …

Local Delivery Of Tumor Associated Macrophage Immunotherapy For The Treatment Of Metastases To The Lungs, Sulaiman Alhudaithi

Theses and Dissertations

Metastases are the leading cause of cancer-related deaths, and the lungs are one of the primary sites of metastases from several malignancies. Existing therapies fail to entirely eradicate tumors that disseminate and reside in lungs; therefore, patient prognosis significantly worsens. Conventional therapies utilized to treat lung tumors such as chemotherapy are administered systemically and typically exhibit poor lung biodistribution profiles, leading to many undesirable off target effects and suboptimal drug concentration in the tumor, which may promote resistance, further compromising the quality of life of secondary lung cancer patients. Immune cells that infiltrate the tumor microenvironment (TME) play a central …

Overcoming Mechanisms Of Acquired And Innate Doxorubicin Resistance Using Nanomedicine And Tumor-Associated Macrophage Immunotherapy, Rashed M. Almuqbil

Theses and Dissertations

ABSTRACT

Overcoming Mechanisms of Acquired and Innate Doxorubicin Resistance Using Nanomedicine and Tumor-Associated Macrophage Immunotherapy

By Rashed M. Almuqbil, Pharm.D.

Director: Sandro R.P. da Rocha, PhD

Cancer is a leading cause of death worldwide. The available treatment for solid tumors may include surgery, radiotherapy, immunotherapy, and chemotherapy or a combination of all those regimens. Chemotherapy is widely used in the treatment of both lung cancers and breast cancer, including metastases, irrespective of type and stage. The poor rates of survival can be attributed to late diagnosis, and due to the development of acquired and innate chemoresistance. Lung tumors are intrinsically …

Continuous Manufacturing Of Pharmaceuticals Using Novel Platforms, Sarah S. Aboelela

Theses and Dissertations

Pharmaceuticals have been synonymously manufactured in a centralized, batch mode with less attention to process and formulation understanding. However, due to rising drug costs, shortages, and robustness issues, in addition to the alarming lack of flexibility and agility, regulatory agencies have pushed towards switching to continuous processes. They believed in continuous manufacturing, providing cleaner, flexible, and more efficient processes. Hence, it was foreseen to reduce development and manufacturing costs, time, and environmental impact and ensured drug product quality. Over the last two decades, continuous manufacturing quality, environmental, and economic advantages have been evident through many case studies and approved products …

Standardization Of E-Cigarette Research: Addressing The Analysis Of Total Nicotine And Free Base Nicotine In E-Cigarettes, Vinit Gholap

Theses and Dissertations

Electronic cigarettes (e-cigarettes) are one of the major sources of exposure to nicotine, an addictive chemical. Since 2016, the Food and Drug Administration (FDA) has started regulating these products under the Tobacco Control Act yet, specifications about the nicotine content in these products have not been established. In e-cigarettes, nicotine concentration ranges from 0 to >50mg/mL. Additionally, several e-cigarette related parameters have been identified which can affect nicotine delivery to users. Of these factors, nicotine forms (protonated and free base) have been found to play a significant role in nicotine absorption profiles yet, a limited and contradictory research is available …

Formulation, Characterization And Pharmacokinetic Modelling Of Excipient Enhanced Growth Spray-Dried Inhalation Powders, Serena Bonasera

Theses and Dissertations

The overall aim of this research project was to evaluate effects of spray drying parameters and storage conditions on solid-state characteristics and aerosol performance of excipient enhanced growth (EEG) powders and to formulate a stable and highly dispersible tobramycin EEG powder to be delivered to pediatric cystic fibrosis subjects using a novel positive pressure dry powder inhaler.

Micrometer-sized albuterol sulfate EEG powders were produced using a medium-sized nebulizer and optimized spray drying conditions. Using trileucine as the dispersion enhancer improved the aerosol performance but showed increased moisture absorption compared to the L-leucine formulation.

The optimized spray drying conditions were then …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Late-Stage Product Development And Approvals By Biotechnology Companies After Initial Public Offering, 1997-2016, Laura M. M. Mcnamee, Ekaterina Galkina Cleary, Sunyi Zhang, Usama Salim, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Purpose: This work describes the late-stage product portfolios of the biotechnology companies that completed initial public offerings (IPOs) from 1997 to 2016. We asked whether these emerging companies continue to develop innovative, biologic products and produce the innovation promised by the early biotechnology industry.

Methods: We identified therapeutic products that reached Phase III development from 1997 to 2016, the characteristics of the products, the dates of the initiation of Phase III and product approval, proxy indicators of the innovativeness of each product, and the contribution of each biotechnology company. Companies were characterized by IPO window and clinical status of the …

Understanding The Impact Of Solvents In Oral Solid Dosage Formulation And Process Development, Matthew Kyle Defrese

Theses and Dissertations--Pharmacy

The successful delivery of chemical compounds for the purpose of therapeutic treatments and prophylactics is a substantial undertaking in modern drug development. Notably, the adoption of high throughput screening techniques has led to the proliferation of poorly water soluble and/or highly potent molecules which further complicate development activities. Spray dried amorphous solid dispersions are an increasingly important formulation strategy to overcome solubility issues while wet granulation approaches are the method of choice for the preparation of highly potent APIs in oral solid dosage forms.

A common connection between these critical techniques is their reliance on solvent-based processing that can often …

Preclinical Pharmacokinetic Studies Of Pterostilbene, And Its Human Pharmacokinetic Prediction Using Physiologically Based Pharmacokinetic Modeling, Palak S. Phansalkar

Theses and Dissertations

This dissertation research aimed to determine the preclinical pharmacokinetics of pterostilbene in vitro and develop a physiologically based pharmacokinetic (PBPK) model to simulate the animal and human PK profiles for pterostilbene. The in vitro PK characteristics of pterostilbene, including Caco-2 cell permeability, plasma protein binding, and metabolic stability were determined using rat and human intestinal & hepatic S9 subcellular fractions. The in vitro metabolic parameters determined in rat subcellular fractions were extrapolated to in vivo values to predict the oral bioavailability (F_oral) in rats. The predicted F_oral was found to be 43.0 %, which is similar to …

De Novo Prediction Of Drug–Target Interactions Using Laplacian Regularized Schatten P-Norm Minimization, Gaoyan Wu, Mengyun Yang, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

In pharmaceutical sciences, a crucial step of the drug discovery is the identification of drug–target interactions (DTIs). However, only a small portion of the DTIs have been experimentally validated. Moreover, it is an extremely laborious, expensive, and time-consuming procedure to capture new interactions between drugs and targets through traditional biochemical experiments. Therefore, designing computational methods for predicting potential interactions to guide the experimental verification is of practical significance, especially for de novo situation. In this article, we propose a new algorithm, namely Laplacian regularized Schatten p-norm minimization (LRSpNM), to predict potential target proteins for novel drugs and potential drugs for …

Social Media Self-Regulation And The Rise Of Vaccine Misinformation, Ana Santos Rutschman

All Faculty Scholarship

This essay examines the main characteristics and shortcomings of mainstream social media responses to vaccine misinformation and disinformation. Parts I and II contextualize the recent expansion of vaccine information and disinformation in the online environment. Part III provides a survey and taxonomy of ongoing responses to vaccine misinformation adopted by mainstream social media. It further notes the limitations of current self-regulatory modes and illustrates these limitations by presenting a short case study on Facebook—the largest social media vehicle for vaccine-specific misinformation, currently estimated to harbor approximately half of the social media accounts linked to vaccine misinformation. Part IV examines potential …

A Semiparametric Modeling Approach For Analyzing Clinical Biomarkers Restricted To Limits Of Detection, Sandipan Dutta, Susan Halabi

Mathematics & Statistics Faculty Publications

Before biomarkers can be used in clinical trials or patients' management, the laboratory assays that measure their levels have to go through development and analytical validation. One of the most critical performance metrics for validation of any assay is related to the minimum amount of values that can be detected and any value below this limit is referred to as below the limit of detection (LOD). Most of the existing approaches that model such biomarkers, restricted by LOD, are parametric in nature. These parametric models, however, heavily depend on the distributional assumptions, and can result in loss of precision under …

Investigations On Novel Cyp26a1/B1 Inhibitor, Dx308: Using Atra Response As A Theraputic Target For Traumatic Brain Injury And Parkinson’S Disease, Jacob Morgan Leatherwood

Graduate Student Theses, Dissertations, & Professional Papers

Neurodegenerative diseases (NDs) take a wide spectrum of pathologies and have a tendency to present themselves later in life. Neurodegenerative diseases affect 6 million Americans annually with ~1 million currently living with Parkinson’s disease (PD). One of the greatest contributors to the pathogenesis of neurodegenerative diseases is the occurrence of a traumatic brain injury (TBI) during life.

All-trans-retinoic acid (atRA) is the active metabolite of Vitamin A. The retinoic acid pathway is known to be activated following TBI and is reduced in PD patients. Previous studies found a decrease in inflammation and behavioral deficits following administration of Vitamin …

Investigation Of Novel Mitoneet Ligand Nl-1 As A Therapeutic For Cerebral Ischemia And Reperfusion Injury, Pushkar Saralkar

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cerebral ischemia reperfusion injury, a common type of stroke, is a neurodegenerative disorder which is the leading cause of permanent disability in the United States. The underlying pathophysiology of ischemic stroke involves an occlusion in the vasculature supplying oxygen and glucose to the brain tissue, leading to infarction and eventual necrosis in the brain. MitoNEET is an outer mitochondrial protein that plays a role in the cellular bioenergetics and its redox physiology. Although its endogenous ligands are under investigation, mitoNEET binds molecules with a thiazolidinedione moiety, such as NL-1. This dissertation investigates NL-1 as a potential cytoprotective agent, and its …

Potential Of Jamu In Nanotechnology Perspective As An Alternative Treatment For Covid-19, Dhadhang Wahyu Kurniawan, Azis Ikhsanudin

Pharmaceutical Sciences and Research

The world seems to be recovering at this time, especially because of the 2019 global coronavirus disease pandemic (COVID-19) caused by the Coronavirus 2 virus (SARS-CoV-2). This virus is similar to other β-coronaviruses through several steps to enter and bind angiotensin-converting enzyme 2 (ACE2) as the main receptor. This binding, particularly in the respiratory epithelium and alveoli of the lungs, affects harmony in human host cells. No specific vaccines and antivirals are available to date as drug investigations are still ongoing. However, many Indonesians consume herbal medicine, especially 'empon-empon' containing the Zingiberaceae family, to protect their health from COVID-19. So …

Antioxidant And Antiaging Assays Of Ageratum Conyzoides (L.) Ethanolic Extract, Afifah B. Sutjiatmo, Novi Edriayani, Tira Endang Mulyasari, Faizal Hermanto, M. Fahrauk, Elin Y. Sukandar, Hanna Sari Widya Kusuma, Rizal Rizal, Wahyu Widowati

Pharmaceutical Sciences and Research

The declining ability of tissues to repair or replace themselves and maintain their structure and normal function is called aging. Aging is caused by free radical that can induce the activation of elastase and collagenase. Ageratum conyzoides (L.) or known as Babadotan is a medicinal plant that has been reported to be a good source of antioxidants that also inhibit aging process. The purpose of this research is to evaluate the antioxidant and antiaging properties of Babadotan Ethanolic Extract (BEE). Franswoth method was used to determine the phytochemical assay of BEE. Measurement of 2,2-diphenyl 1-picrylhydrazyl (DPPH) scavenger was used for …

Evaluation Of Antipsychotic Activity Of Ethanolic Bark Extract Of Myrica Esculenta In Rats, Biswash Sapkota, Ankit Acharya, Bishal Dangi, Annegowda Hv

Pharmaceutical Sciences and Research

The antipsychotic properties of Myrica esculenta stem bark were evaluated. The stem bark was collected, shade dried, and pulverized. Extraction was carried out with 70% ethanol by occasional shaking. Preliminary phytochemical screening of the extract was investigated in this study. Antipsychotic activity was evaluated against apomorphine-induced stereotypy using cook’s pole climbing apparatus and haloperidol-induced catalepsy models. Bioamine determination of noradrenaline and dopamine was also performed. The extract contains phytochemicals, including glycosides, flavonoids, volatile oils, proteins, saponins, phenolics, and tannins. The result showed decreased apomorphine-induced stereotyped behavior. This study reported significant dose-dependent potentiation of haloperidol-induced catalepsy in rats and a longer …

The Anti-Proliferation Effect Of An Isolated Butanol Fraction Of Tampa Badak (Voacanga Foetida (Bl.) K. Schum) Leaves On Leukemia, Lung, And Cervical Cancer, Adriani Susanty, Dachriyanus Dachriyanus, Yanwirasti Yanwirasti, Fatma Sri Wahyuni, Andisyah Putri Sekar, Nur Alimin, Magdazaleni Magdazaleni, Sri Esky Sofia, Citra Kartika Dewi

Pharmaceutical Sciences and Research

Voacanga foetida (Bl.) K.Schum leaves are known to have cytotoxic activity against blood cancer cells. This study was aimed to determine the potential of an isolated butanol fraction of Voacanga foetida (Bl.) K.Schum leaves (Tb3 compound) in inhibiting the proliferation of several cancer cells, including leukemia (K562), lung cancer (A549), and cervical cancer (He-La) using the dye exclusion method. We found that the percentage of anti-proliferation of the Tb3 compound was increased in a dose-dependent manner, where it showed 83% (K562), 72.3% (He-La), and 70.7% (A549) inhibition at higher concentration. These values were relatively higher compared to doxorubicin as a …

Inhibitory And Anti-Biofilm Effects Of Orthoshipon Aristatus Against Candida Albicans, Ratika Rahmasari, Ananda Hanny Chairunissa, Marina Ika Irianti, Roshamur Cahyan Forestrania, Ayun Erwina Arifianti, Herman Suryadi, Juliann Nzembi Makau, Ibrahim Jantan, Berna Elya

Pharmaceutical Sciences and Research

There are increasing number of reports on Candida albicans developing resistance to available anti-fungal drugs. Thus, there is an urgent need to discover new agents for treatment of candidiasis. The alcoholic extracts of Orthoshipon aristatus have been shown to exhibit antifungal activity against C. albicans by using the agar diffusion and broth microdilution methods. However, the underlying mechanisms of anti-C. albicans effect of O. aristatus have not been well understood. This study was aimed to evaluate the cytotoxic and anti-biofilm effects of the n-hexane and ethanol extracts of purple and white varieties of O. aristatus leaves …

Fractionation Of Citronella Oil And Identification Of Compounds By Gas Chromatography-Mass Spectrometry, Yelfi Anwar, Victor S. Siringoringo

Pharmaceutical Sciences and Research

Citronella oil is one of the most important essential oils and is widely used in the pharmaceutical, cosmetic and food industries. However, the selling price of citronella oil is still low, so efforts are needed to increase its added value by isolating the active components such as citronellal, citronellol and geraniol. This study aims to isolate the active ingredients of citronella oil that have higher economic added value. Citronella oil was obtained by the process of distillation of Cymbopogon nardus (L.) Rendle leaves. The essential oil was then fractionated by a vacuum fractionation process. The essential oil fraction was identified …

Antifungal Activity Of Polyscias Scutellaria Fosberg Leaves Against Candida Albicans, Nada Marcha Putri, Jasmine Regita Putri, Berna Elya, Robiatul Adawiyah

Pharmaceutical Sciences and Research

Polyscias scutellaria Fosberg is one of the indigenous plants from Indonesia that widely used as folk medicines for several illnesses. The leaves of P. scutellaria were previously studied as an antimicrobial agent. Nonetheless, this theory of antifungal activity has never been scientifically verified. This study aimed to evaluate the antifungal activity of P. scutellaria against Candida albicans. The leaves of P. scutellaria were macerated using an ethanol solvent. Then, the extract was evaporated and dissolved by 1% DMSO into different concentrations (100 μg/mL, 200 μg/mL, 400 μg/mL, 800 μg/mL, 1600 μg/mL, 3200 μg/mL, and 6400 μg/mL). Fluconazole, as a …

Pharmacological Characterization Of Novel Serotonin Transporter Inhibitors Identified Through Computational Structure-Based Virtual Screening, Michael Wasko

Electronic Theses and Dissertations

Depression is a mental health disorder affecting greater than 350 million people worldwide with roughly 7% of the United States population diagnosed as of 2017. The selective serotonin reuptake inhibitors (SSRIs) have been the mainstay of pharmacotherapies for depression for the last 40 years. The SSRIs target the serotonin transporter (SERT), a monoamine transporter (MAT) responsible for terminating serotonergic neurotransmission. The SSRIs are not perfect therapeutics and suffer from delayed response times, inconsistent efficacy among patients, and often produce intolerable side effects. Therefore, a strong need exists to develop new antidepressants that are more efficacious and have fewer adverse effects. …