Pharmaceutics and Drug Design Commons^™

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) …

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 …

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 …

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 …

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 …

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 …

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 …