Pharmaceutics and Drug Design Commons^™

Preliminary Characterization, Antioxidant And Antiproliferative Properties Of Polysaccharide From Caulerpa Taxifolia, Ariane Marie Bayro, Joanne Katherine Manlusoc, Renaliza Alonte, Catherine Caniel, Patrick Conde, Carlo Embralino

Pharmaceutical Sciences and Research

Macroalgae are abundant sources of bioactive polysaccharides and prospective candidates for effective and non-toxic substances. This study aims to preliminary characterize and determine the in vitro antioxidant activity and cancer cell growth inhibitory activity against human lung adenocarcinoma cell (A549) of the polysaccharide from an invasive green alga, Caulerpa taxifolia. Crude polysaccharide (CP) was extracted from the dried algal sample of C. taxifolia by hot water extraction followed by absolute ethanol precipitation. CP was subjected to preliminary chemical characterization, including protein, carbohydrate, and sulfate content analysis by Kjeldahl titrimetry, acid hydrolysis, gravimetry, and ashing-acid water digestion ion chromatography, respectively. …

Suppression Of Human Coronavirus 229e Infection In Lung Fibroblast Cells Via Rna Interference, Hamidreza Montazeri Aliabadi, Jennifer Totonchy, Parvin Mahdipoor, Keykavous Parang, Hasan Uludağ

Pharmacy Faculty Articles and Research

Despite extensive efforts to repurpose approved drugs, discover new small molecules, and develop vaccines, COVID-19 pandemic is still claiming victims around the world. The current arsenal of antiviral compounds did not perform well in the past viral infections (e.g., SARS), which casts a shadow of doubt for use against the new SARS-CoV-2. Vaccines should offer the ultimate protection; however, there is limited information about the longevity of the generated immunity and the protection against possible mutations. This study uses Human Coronavirus 229E as a model coronavirus to test the hypothesis that effective delivery of virus-specific siRNAs to infected cells will …

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 …

Formulation And Characterization Of Beeswax/Rosemary Oil Nanostructured Lipid Carrier For Drug Delivery System, Mohd Latif Farhanim

Student Works (2020-2029)

A stable colloidal suspension of nanostructured lipid carriers (NLCs) was synthesized from natural source of lipid. The toxicity and insolubility of drugs in water remain a significant problem and has led to the development of food-grade drug delivery systems such as nanostructured lipid carriers (NLCs). NLCs composing various amount of beeswax (BW), rosemary oil (RO) and poloxamer 188 (P188) were prepared by melt-emulsification combined with ultrasonication method. The physicochemical properties of NLC also were determined. Optimization of the formulation (F) was performed based on the criteria of stability. Formulation with the smallest particle size and highest magnitude of zeta potential …

[(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 …

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 …

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 …

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 …

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 …

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 …

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 …

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) …