Lipids Commons^™

Exogenous Surfactant As A Delivery Vehicle For Intrapulmonary Therapeutics, Brandon J. Baer

Electronic Thesis and Dissertation Repository

As an organ system, the lung has unique advantages and disadvantages for direct drug delivery. Its contact with the external environment allows for the airways to be easily accessible to intrapulmonary delivery. However, its complex structure, which divides into more narrow airways with each branch, can make direct delivery to the remote alveoli challenging. The objective of this thesis was to overcome this issue by using exogenous surfactant, a lipoprotein complex used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics. It was hypothesized that therapeutics administered with a surfactant vehicle would display enhanced delivery to the …

Characterization Of Lamellar Liquid Crystal Emulsifiers In Topical Creams Containing A Novel Solvent, Melinda Joanna Sutton

MSU Graduate Theses

Diethylene glycol monoethyl ether (DEGEE) is a promising solvent component in topical cream formulations due to its superior solubilizing abilities with certain active pharmaceutical ingredients. One of the goals of this study is to characterize the effects of pH on the physical and chemical stabilities of topical cream formulations containing particularly high concentrations of DEGEE by characterizing a full topical pH profile of 3.5 – 9.0. The second goal is to evaluate the presence, amount, and characteristics of lyotropic liquid crystals (LLCs), molecularly structured in a lamellar phase, in a model cream emulsion utilizing polarized light microscopy (PLM). The presence …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

A Robust Delivery System For Rna Therapeutics, Suleyman Bozal

University Scholar Projects

The field of RNA therapeutics is currently undergoing both transformation and expansion. Specifically, research in lipid nanoparticle (LNP) based RNA therapeutics is gaining significant traction. Other research into mechanisms of gene regulation and manipulation, including siRNA and the CRISPR/Cas9 system have demonstrated the potential of RNA-based disease treatment. This work identifies a delivery system which can regulate expression of green fluorescent protein (GFP) in human embryonic kidney cells (HEK293) stably expressing GFP.

Analysis of siRNA-induced gene knockdown demonstrates that the current siRNA-LNP formulation is equally as effective as a commercially available transfection reagent, Lipofectamine RNAiMAX (RNAiMAX), which is designed specifically …

A Robust Delivery System For Rna Therapeutics, Suleyman Bozal

Honors Scholar Theses

The field of RNA therapeutics is currently undergoing both transformation and expansion. Specifically, research in lipid nanoparticle (LNP) based RNA therapeutics is gaining significant traction. Other research into mechanisms of gene regulation and manipulation, including siRNA and the CRISPR/Cas9 system have demonstrated the potential of RNA-based disease treatment. This work identifies a delivery system which can regulate expression of green fluorescent protein (GFP) in human embryonic kidney cells (HEK293) stably expressing GFP.

Analysis of siRNA-induced gene knockdown demonstrates that the current siRNA-LNP formulation is equally as effective as a commercially available transfection reagent, Lipofectamine RNAiMAX (RNAiMAX), which is designed specifically …

Gene Expression Microarray Data From Human Microvascular Endothelial Cells Supplemented With A Low Concentration Of Niacin, Nica M. Borradaile, Jennifer M. Hughes-Large

Physiology and Pharmacology Publications

The systemic lipid modifying drug, niacin, can directly improve human microvascular endothelial cell angiogenic function under lipotoxic conditions, possibly through activation of niacin receptors [1]. Here we provide accompanying data collected using Affymetrix GeneChip microarrays to identify changes in gene expression in human microvascular endothelial cells treated with 10 μM niacin. Statistical analyses of robust multi-array average (RMA) values revealed that only 16 genes exhibited greater than 1.3-fold differential expression. Of these 16, only 5 were identified protein coding genes, while 3 of the remaining 11 genes appeared to be small nuclear/nucleolar RNAs. Altered expression of EFCAB4B, …

The Effect Of All-Trans Retinoic Acid And Fatty Acids On Mcf-7 Breast Cancer Cell Progression, David Brown

David C. Brown

Vitamin A metabolites and retinoids may slow the progression of breast cancer and elicit anti-neoplastic properties similar to those of omega-3 fatty acids. Studies using animal models show a decrease in the incidence, growth and metastisis of mammary tumors in the presence of specific fatty acids. This effect is also seen with use of retinoids, specifically all-trans retinoic acid (AtRA). Thus, fatty acids may also alter retinoid homeostasis in mammary carcinoma cells (MCF-7s). The potential for inter/co dependency among fatty acids and retinoids is considerable, and here it has been hypothesized that a decrease in cancer progression will occur in …

The Synthesis And Study Of The Biological And Colloidal Properties Of Bolaamphiphiles, Louis M. Damiano

Senior Honors Projects, 2010-2019

Over the past decade, antibiotic resistant bacteria have caused infections in patients throughout the world.^[1] The rise in antibiotic resistance is primarily due to the misuse and overuse of antibiotics. ^[1] To counter the increase in antibiotic resistance, infection control mechanisms have been aggressively researched in recent years. In particular, drug delivery has become a focal point to fight antibiotic resistant infections.^[2] Amphiphiles have a wide range of applications in the clinical setting, including the ability to inhibit bacterial transference because of their bactericidal activity. ^[3] Bolaamphiphiles are a subclass of amphiphiles that possess two or more hydrophilic …

Design, Synthesis And Biological Evaluation Of Novel Compounds With Cns-Activity Targeting Cannabinoid And Biogenic Amine Receptors, Alexander M. Sherwood

University of New Orleans Theses and Dissertations

This work seeks to contribute to the discipline of neuropharmacology by way of structure activity relationship from the standpoint of an organic chemist. More specifically, we sought to develop robust synthetic methodology able to efficiently produce an array of compounds for the purpose of systematic evaluation of their interaction with specific sights within the central nervous system (CNS) in order to better understand the mind and to develop drugs that may have beneficial effects on neurological function.

The focus of these studies has been toward the development of novel molecules, using a structure-activity relationship approach, that exhibit binding affinity at …

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall

Dissertations & Theses (Open Access)

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …

The Effect Of All-Trans Retinoic Acid And Fatty Acids On Mcf-7 Breast Cancer Cell Progression, David A. Brown

Master's Theses

Vitamin A metabolites and retinoids may slow the progression of breast cancer and elicit anti-neoplastic properties similar to those of omega-3 fatty acids. Studies using animal models show a decrease in the incidence, growth and metastisis of mammary tumors in the presence of specific fatty acids. This effect is also seen with use of retinoids, specifically all-trans retinoic acid (AtRA). Thus, fatty acids may also alter retinoid homeostasis in mammary carcinoma cells (MCF-7s). The potential for inter/co dependency among fatty acids and retinoids is considerable, and here it has been hypothesized that a decrease in cancer progression will occur in …