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Full-Text Articles in Pharmaceutics and Drug Design

A Robust Delivery System For Rna Therapeutics, Suleyman Bozal May 2019

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 ...


A Robust Delivery System For Rna Therapeutics, Suleyman Bozal May 2019

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 ...


Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti May 2018

Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti

GSBS Dissertations and Theses

Extracellular vesicles (EVs), exosomes and microvesicles, transfer endogenous RNAs between neurons over short and long distances. We have explored EVs for siRNA delivery to brain. (1) We optimized siRNA chemical modifications and siRNA conjugation to lipids for EV-mediated delivery. (2) We developed a GMP-compatible, scalable method to manufacture active EVs in bulk. (3) We characterized lipid and protein content of EVs in detail. (4) We established how protein and lipid composition relates to siRNA delivering activity of EVs, and we reverse engineered natural exosomes (small EVs) into artificial exosomes based on these data.

We established that cholesterol-conjugated siRNAs passively associate ...


Lack Of Cross-Reactivity Allergy Following A Switch From Alirocumab To Evolocumab, Matthew D. Stryker, Michael Kane, Robert Busch Oct 2016

Lack Of Cross-Reactivity Allergy Following A Switch From Alirocumab To Evolocumab, Matthew D. Stryker, Michael Kane, Robert Busch

Excerpts in Pharmacy Research Journal

The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene and gain-of-function mutations were first described in 2003. The gain-of-function mutations observed were associated with low-density lipoprotein-cholesterol (LDL-C) levels in the 400’s, in addition to premature cardiovascular disease. Subsequent loss-of-function experiments conducted in mice demonstrated marked reductions in plasma cholesterol levels in the absence of PCSK9. Physiologically, PCSK9 serves as a chaperone protein and functions to reduce low-density lipoprotein (LDL) receptor recycling; consequently, less LDL-C is removed from circulation and serum lipid concentrations become elevated. Inhibition of PCSK9 prevents LDL receptor degradation and preserves receptor recycling to the hepatocyte surface ...


Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown Jan 2015

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity ...


Design, Synthesis And Biological Evaluation Of Novel Compounds With Cns-Activity Targeting Cannabinoid And Biogenic Amine Receptors, Alexander M. Sherwood May 2014

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 Jan 2014

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 ...