Engineering Commons^™

Levofloxacin Incorporated Extracellular Matrix Nanoparticles For Pulmonary Cystic Fibrosis Infections, Raahi Patel

Theses and Dissertations

Cystic fibrosis (CF) is a progressive genetic disorder that affects around 40,000 people in the United States. CF is characterized by a mutation in the CFTR protein that causes dysregulated ion transport across epithelial cells, producing viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in CF patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX) that functions to inhibit bacterial replication, but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled …

Advanced Processing Techniques For Electrospun Nanofibers: Investigating Annealing And Laser Zone-Drawing Effects On Material Characteristics, Matthew D. Flamini

Theses and Dissertations

Electrospun nanofibers hold potential for a wide range of commercial and scientific applications; however, their properties must be optimized through post-processing treatments to achieve optimal performance. This dissertation investigates the effects of annealing and laser zone-drawing on electrospun nanofiber properties. Annealing polycaprolactone nanofibers at 70°C results in the highest rate of crystallization and molecular alignment, impacting long-term stability and mechanical properties. A multivariate linear model incorporating crystallinity and molecular alignment predicts the material properties resulting from annealing under different conditions. Laser zone-drawing experiments reveal that polylactide fiber thinning under laser irradiation primarily occurs due to drawing rather than ablation. Steady-state …

Polyethyleneimine Shell Nucleic Acid Nanostructures From Gold Nanoparticle Template For Chemotherapeutic Drug Delivery, Brendan Guy Rucci

Theses and Dissertations

The next generation of anticancer agents will emerge from rationally designed nanostructured materials. This work involved the synthesis and characterization of novel hollow DNA-conjugated gold nanoparticles (DNA-AuNPs) for controlled drug delivery. Polyethyleneimine (PEI) was bound to citrate-capped AuNPs, forming polymer-shell nanoparticles. Dissolution of the gold core via iodine formed hollow core polymeric nanoparticles (HCPPs) and a high density of DNA (85 molecules/particle) containing daunorubicin was conjugated. Particles were spherical with an average diameter of 105.7±17.3 nm and zeta potential of 20.4±3.54 mV. We hypothesize the DNA backbone electrostatically condensed to the primary amines on the surface of the particle toroidally, …

Dendrimer-Based Drug Delivery Systems: History, Challenges, And Latest Developments, Juan Wang, Boxuan Li, Li Qiu, Xin Qiao, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

Since the first dendrimer was reported in 1978 by Fritz Vögtle, dendrimer research has grown exponentially, from synthesis to application in the past four decades. The distinct structure characteristics of dendrimers include nanoscopic size, multi-functionalized surface, high branching, cavernous interior, and so on, making dendrimers themselves ideal drug delivery vehicles. This mini review article provides a brief overview of dendrimer's history and properties and the latest developments of dendrimers as drug delivery systems. This review focuses on the latest progress in the applications of dendrimers as drug and gene carriers, including 1) active drug release strategies to dissociate drug/gene from …

Synergistic Anticancer Response Of Curcumin And Piperine Loaded Lignin-G-P (Nipam-Co-Dmaema) Gold Nanogels Against Glioblastoma Multiforme, Xinyi Zhao, Bilal Javad, Daxing Cui, James Curtin, Furong Tian

Articles

Glioblastoma multiforme (GBM) is the most aggressive and commonly diag- 11 nosed brain cancer and presents a strong resistance to routine chemotherapeutic drugs. 12 The present study involves the synthesis of Lignin-g- p (NIPAM-co-DMAEMA) gold 13 nanogel, loaded with curcumin and piperine to treat GBM. The application has three 14 functions: (1) overcome the limitations of biodistribution, (2) enhance the toxicity of an- 15 ticancer drugs against GBM, (3) identify the uptake pathway. Atom transfer radical 16 polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with 17 the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and …

Glial Endothelial Brain Cell Co-Cultures For Testing Signaling Response And Delivery Of Novel Materials Across Blood Brain Barrier, Neela Prajapati

Master's Theses

The brain accounts for 20% of overall energy metabolism in the body though it just comprises 2% of the total body mass but has a limited capacity of storing energy unlike other critical organs in the body such as the heart and liver. This energy along with oxygen and nutrients is supplied by cerebral blood flow (CBF), any interruption of which can cease the brain function within seconds with a potential irreversible neuronal injury, within minutes. Vascular cells along with astrocytes and neurons are a part of a recently developed concept known as the Neurovascular Unit responsible for Neurovascular coupling …

Glial Endothelial Brain Cell Co-Cultures For Testing Signaling Response And Delivery Of Novel Materials Across Blood Brain Barrier, Neela Prajapati

Doctoral Dissertations

The brain accounts for 20% of overall energy metabolism in the body though it just comprises 2% of the total body mass but has a limited capacity of storing energy unlike other critical organs in the body such as the heart and liver. This energy along with oxygen and nutrients is supplied by cerebral blood flow (CBF), any interruption of which can cease the brain function within seconds with a potential irreversible neuronal injury, within minutes. Vascular cells along with astrocytes and neurons are a part of a recently developed concept known as the Neurovascular Unit responsible for Neurovascular coupling …

Polymer Microparticles For Encapsulation And Presentation Of Anti-Inflammatory Agents For Inflammatory Diseases, Christopher Isely

Theses and Dissertations

Inflammatory diseases have a huge economic impact on the healthcare system. Incidence of obesity and muscle atrophy, two high profile inflammatory diseases, continues to increase. Anti-inflammatory agents are potential therapeutics for these diseases. Resveratrol is a polyphenol that has anti-inflammatory effects; however, resveratrol suffers from low bioavailability and hasn’t had impressive clinical results when delivered orally. Mannose is a monosaccharide that also has anti-inflammatory effects, however, effects are highest when mannose is presented on the surface of a support the size of a bacteria. Incorporation of resveratrol and mannose into biodegradable polymer microparticles could be a feasible approach to overcome …

Development Of The Cell-Free Protein Biomanufacturing Platform For The Therapeutic Human Protein Production And The Topical Delivery Applications Using The Nanosized Hydrogel System, Jeehye Kim

LSU Doctoral Dissertations

Proteins are highly structural polymers, performing an enormous range of roles within organisms. Unlike synthetic polymers, proteins have a significant hierarchical ordering that can be disrupted by many environmental factors, which limits the scale-up manufacturing capability as well as the utilization of proteins as therapeutic agents. In this study, the Cell-Free Protein Synthesis (CFPS) system was developed to enhance the production capacity and applications of the therapeutic proteins. The CFPS is an advanced biosynthetic and genetic-engineered system. It enables the efficient production of proteins when the conventional cell-based protein synthesis systems cannot be applied, and when sophisticated control is required …

Additive Manufacturing In Personalized Medicine: Patient-Customized Solid Dose Medicines, And Patient-Customized Wound Care Device, Amir Najarzadeh

Theses and Dissertations--Mechanical Engineering

Personalized Medicine - from a one-size fits all to a tailored approach is the future in pharmaceutical therapeutics and medical applications. The aim of this study is demonstrate additive manufacturing in two personalized medicine applications: 1. Patient- customized solid dose medicines, and 2. Patient-customized wound care device. The aim of the first application is to develop an inexpensive and accurate method to design and fabricate patient-customized tablets. Particularly this paper focuses on fabricating and dose controlling of patient-customized extended release prednisolone-poly(vinyle alcohole) PVA. Dry-Blending, Wet Granulation, Extrusion, Spherionization, Hot melt extrusion (HME) was adopted to produce drug loaded prednisolone-PVA filaments …

Complementary Techniques To Study The Behavior Of Water And The Effect On Diffusion And Degradation In Hydrogels, Paige Rockwell

Master’s Theses

Hydrogels exhibit biocompatibility in a range of biomedical applications, including drug delivery. This thesis aims to develop complementary techniques to measure the diffusion and degradation behaviors within an injectable, hydrolytically degradable hydrogel, formed via the covalent crosslinking of ethoxylated trimethylolpropane tri-3- mercaptopropionate (ETTMP) and poly(ethylene glycol) diacrylate (PEGDA), to determine its suitability as a drug delivery matrix. The characterization of water as either free, within the network openings of the hydrogel, or bound, tightly associated with the polymer chains, was determined using differential scanning calorimetry (DSC). The mobility of each type of water within the hydrogels was determined via nuclear …

Alternative Epinephrine Auto-Injector, Joshua Wong, Uriel Nieves-Cruz, Tara Howard

Biomedical Engineering

Project: Alternative Epinephrine Injector started as a solution for Bianca Aleman’s little brother however the scope has evolved to include the many millions of individuals across the world who struggle with a life-threatening allergen. The stakeholders of this project are Cal Poly and Dr. Michael D. Whitt. Our goals are the following:

● Develop a foolproof method of injection that consistently delivers a dosage of epinephrine

● Be equal or less than the current size of an EpiPen (6 in)

● Be easy to transport or store when not-in-use

● Create an isolated environment where the epinephrine will not be …

A Framework For Heterologous Biosynthesis Of Natural Products In Mammalian Cells Via Polymer-Mediated Transfections, Logan Warriner

Theses and Dissertations--Chemical and Materials Engineering

With the promise to treat a multi-faceted list of serious inherited and acquired diseases, such as cancer, neurodegenerative and infectious diseases, and inherited genetic indications, gene therapy has continued to push the boundaries of traditional medicine since its earliest implementation. While much progress has been made, clinical success has largely remained elusive. Immunogenicity, difficulty producing commercially relevant quantities, and having a limited genetic payload still limits the ability of viruses to act as directed delivery agents for genetic material. As such, researchers have turned to cationic synthetic materials as a means of delivering nucleic acids, which can circumvent the immune …

A Ph-Sensitive Delivery System For The Prevention Of Dental Caries Using Salivary Proteins, Yi Zhu

Electronic Thesis and Dissertation Repository

Dental caries remains one of the most common chronic diseases worldwide. Salivary proteins such as histatins have demonstrated biological functions directly related to tooth homeostasis and prevention of dental caries. However, histatins are susceptible to the high proteolytic activities in the oral environment. Therefore, pH-sensitive chitosan nanoparticles (CNs) have been proposed as potential carriers to target major oral diseases that occur under acidic conditions (e.g. dental caries and dental erosion). Four different types of chitosan polymers were investigated and the optimized CNs successfully loaded histatin 3 and released it selectively under acidic conditions. Through loading the survival time of histatin …

Engineering Of Gold Nanoparticles For Drug Delivery, Fangchao Liu

Wayne State University Dissertations

Due to their ease of synthesis, versatile surface chemistry, ease of imaging, and biocompatibility, gold nanoparticles (AuNPs) are employed as drug delivery devices in the treatment of respiratory problems associated with spinal cord injury (SCI). We have developed a method for the synthesis of a tripartite nanoconjugate comprised of an AuNP drug carrier chemically conjugated to a transporter protein (wheat germ agglutinin coupled to horseradish peroxidase or WGA-HRP) and to potent SCI drugs. The therapeutic efficacy and biodistribution were studied in a validated animal model. Our results show that a single administration of the nanoconjugate improved diaphragmatic activity at a …

Development And Characterization Of Multi-Crosslinking Injectable Hydrogels For Use In Cell And Drug Delivery, Jennifer Etter

Graduate College Dissertations and Theses

Injectable hydrogels are important for use in tissue engineering due to their permeability and biocompatibility. Those that have shear thinning properties allow for minimally-invasive surgical procedures and a way to administer bioactive agents, and therapeutic cells by injection. Currently available injectable hydrogels have a single or dual input/stimulus for crosslinking which limits the range of mechanical properties and often utilize potentially toxic ultraviolet radiation that reduces viability of injected cells. To overcome these shortcomings, a tri-stimuli-responsive alginate-based injectable hydrogel was developed based on: 1) supramolecular complex formation between β-cyclodextrin (β-CD) conjugated alginate and thermo-responsive tri-block Pluronic® copolymers, 2) visible light …

The Effectiveness Of Localized Ultrasound And Aptamer Surface Modification On Nanoemulsions For Drug Delivery To Spheroids., Daniel A. Hodge

Electronic Theses and Dissertations

Cancer is a group of diseases that affects 1.6 million and kills nearly 600,000 Americans each year. The National Cancer Institute defines it as “diseases in which abnormal cells divide without control and can invade nearby tissues” and it is often treated with one or more of the following: chemotherapy, radiation, surgery. The expense for these treatments is expected to rise to $156 billion by 2020. Localized delivery can improve effectiveness and cancer survival rates, decrease the cost of treatment, and decrease the side effects of chemotherapy. This paper addresses models for this localized delivery through nanoemulsions. Nanoemulsions are a …

Structure-Property Relationships In Novel Electrospun Composites For Advanced Applications, Melodie Lawton

Dissertations - ALL

Active polymeric materials that alter shape in response to an external stimulus offer unique avenues for the design and study of dynamic structures. This research focused on developing elastomeric polymer composites with multiple functionalities by exploring the design and properties for various applications including controlled drug delivery and shape memory.

The first part of this dissertation describes the fabrication and characterization of a soft, elastomeric polymeric composite with inherent shape memory properties capable of localized, long-term tunable drug release. In Chapter 2, the fibers were loaded with a hydrophilic drug model, Rhodamine B, and embedded within a siloxane-based elastomeric matrix …

Investigation Of The Ms2 Bacteriophage Capsid As An Mri-Capable, Brain-Targeted Nanoparticle Platform, Stephanie M. Curley

Legacy Theses & Dissertations (2009 - 2024)

Novel methods are needed to traverse the blood-brain barrier (BBB) and deliver drugs to specific targets in the brain. To this end, MS2 bacteriophage was explored as a multifunctional transport and targeting vector. The MS2 capsid exterior was modified with two different targeting moieties for delivery across the BBB and targeting specific regions of interest in the brain. Successful modification of MS2 capsids with a brain targeting peptide and NMDAR2D-targeting antibody was confirmed by immunoblotting and fluorescence detection. To measure transport efficiency of MS2 particles across an in vitro BBB model, a highly sensitive RT-qPCR protocol was developed and implemented. …

A Multiscale Modeling Study Of Particle Size Effects On The Tissue Penetration Efficacy Of Drug-Delivery Nanoparticles, Mohammad Aminul Islam, Sutapa Barua, Dipak Barua

Chemical and Biochemical Engineering Faculty Research & Creative Works

Background: Particle size is a key parameter for drug-delivery nanoparticle design. It is believed that the size of a nanoparticle may have important effects on its ability to overcome the transport barriers in biological tissues. Nonetheless, such effects remain poorly understood. Using a multiscale model, this work investigates particle size effects on the tissue distribution and penetration efficacy of drug-delivery nanoparticles.

Results: We have developed a multiscale spatiotemporal model of nanoparticle transport in biological tissues. The model implements a time-adaptive Brownian Dynamics algorithm that links microscale particle-cell interactions and adhesion dynamics to tissue-scale particle dispersion and penetration. The model accounts …

Nanomedicine Drug Delivery Across Mucous Membranes, Michael G. Lancina Iii

Theses and Dissertations

NANOMEDECINE DRUG DELIVERY ACROSS MUCOUS MEMBRANES

By Michael G. Lancina III

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth Univeristy, 2017.

Major Director: Dr. Hu Yang, Associate Professor, Chemical and Life Science Engineering

Control over the distribution of therapeutic compounds is a complex and somewhat overlooked field of pharmaceutical research. When swallowing a pill or receiving an injection, it is commonly assumed that drug will spread throughout the body in a more or less uniform concentration and find its way to wherever it is needed. In …

Potential Applications For Halloysite Nanotubes Based Drug Delivery Systems, Lin Sun

Doctoral Dissertations

Drug delivery refers to approaches, formulations, technologies, and systems for transporting a drug in the body. The purpose is to enhance the drug efficacy and to reduce side reactions, which can significantly improve treatment outcomes. Halloysite is a naturally occurred alumino-silicate clay with a tubular structure. It is a biocompatible material with a big surface area which can be used for attachment of targeted molecules. Besides, loaded molecules can present a sustained release manner in solution. These properties make halloysite nanotubes (HNTs) a good option for drug delivery.

In this study, a drug delivery system was built based on halloysite …

Investigation Of Enzymatically Synthesized Glycogen As A Novel Nanodendrimer For Therapeutic Delivery, Sarah Ann Engelberth

Legacy Theses & Dissertations (2009 - 2024)

The field of medicinal chemistry is ever expanding, designing and discovering new therapeutic strategies. Oftentimes, it is challenging for these therapeutics to undergo clinical translation due to ineffective administration or unwanted toxicity in vivo. As such, drug delivery vehicles are designed to overcome these hurdles, allowing for delivery to the site of action by improving biodistribution, protecting therapeutic cargo, and decreasing toxicity. The work presented here aims to investigate a naturally-derived carbohydrate nanodendrimer, enzymatically synthesized glycogen (ESG) for drug delivery. This nontoxic, highly-branched, glucose-based structure has interior void volumes to allow for cargo encapsulation as well as a large density …

A Theoretical Study Of Polymer Based Drug Delivery Systems, Ebtisam Abdullatif Aldaais

Theses and Dissertations

Polymer nanostructured materials for drug delivery applications have witnessed tremendous progress in recent years due to their vast potential. One-end-grafted polymers can form grafted micelles with specific mechanical properties. Biological conditions can alter these properties resulting in the protection or release of drugs. Charged surfactants can also form micelles in an aqueous solution, which can also be manipulated through special conditions. On the micellar surface, self-organized polyelectrolytes can be stimulated to extend their attached ligands and thus increase the probability of binding to targeted receptors. This thesis focuses on modeling polymer-based drug delivery systems by studying the physical interactions between …

Sustained Dual Drug Delivery Of Anti-Inhibitory Molecules For Spinal Cord Injury Treatment, Thomas Wilems

McKelvey School of Engineering Theses & Dissertations

Regeneration of lost synaptic connections following spinal cord injury (SCI) is limited due to local ischemia, cell death, and an excitotoxic environment, which leads to the development of an inhibitory glial scar surrounding a cystic cavity. Myelin-associated inhibitors (MAIs) and chondroitin sulfate proteoglycans (CSPGs) are major inhibitors to axon growth inhibition found within the glial scar and limit functional recovery. The NEP1-40 peptide competitively binds the Nogo receptor and partially blocks inhibition from MAIs, while chondroitinase ABC (ChABC) enzymatically digests CSPGs, which are upregulated at the site of injury. The first part of this work develops drug delivery systems which …

Engineering Of Lipid Nanoparticles For Advanced Drug Delivery Applications, Stephen L. Hayward

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

‘Nanomedicine’, the application of nanotechnology principles to the field of medicine, has stimulated the development of nano-platforms for next generation drug delivery. By exploiting nanoscale properties of materials to selectively alter intrinsic characteristics of therapeutics, researchers have improved the efficacy and pharmacokinetic profiles for a variety of drug types. Despite preliminary commercial and clinical success, there still remains a need to develop an improved delivery platform that can provide high cargo entrapment, efficient intracellular delivery, evasion of intracellular degradation pathways, and provide cell population specific targeting.

In this study we engineered a nanocarrier system composed of a core bilayer structure …

Efficacy Of A Magnetic Drug Delivery System And Development Of An Orthotopic Lung Tumor Imaging Model, Amber Mcbride

Nanoscience and Microsystems ETDs

The aim of this work was the development of a novel drug delivery vehicle termed nano-in-microparticles (NIMs) to evaluate the magnetic-field dependent targeting of dry powder NIMs administered endotracheally using an ex vivo and in vivo rodent model. NIMs are a novel dry powder drug delivery vehicle containing 70% lactose (w/w), 20% SPIONs (w/w) and 10% fluorescent nanospheres (w/w). Mice were insufflated with NIMs delivery vehicle in the presence of magnetic field dependent targeting to the left ventral lung after thoracotomy; controls were insufflated with the NIMs in the absence of magnetic field dependent targeting. Quantification of deposition of the …

Solute Partitioning In Elastin-Like Polypeptides: A Foundation For Drug Delivery Applications, Eric Helm

ETD Archive

No abstract provided.

Engineering Of Polyamidoamine Dendrimers For Cancer Therapy, Leyuan Xu

Theses and Dissertations

Dendrimers are a class of polymers with a highly branched, three-dimensional architecture comprised of an initiator core, several interior layers of repeating units, and multiple active surface terminal groups. Dendrimers have been recognized as the most versatile compositionally and structurally controlled nanoscale building blocks for drug and gene delivery. Polyamidoamine (PAMAM) dendrimers have been most investigated because of their unique structures and properties. Polycationic PAMAM dendrimers form compacted polyplexes with nucleic acids at physiological pH, holding great potential for gene delivery.

Folate receptor (FRα) is expressed at very low levels in normal tissues but expressed at high levels in cancers …

Synthesis And Evaluation Of Sensitizer Drug Photorelease Chemistry: Micro-Optic Method Applied To Singlet Oxygen Generation And Drug Delivery, Goutam Ghosh

Dissertations, Theses, and Capstone Projects

This thesis summarizes a new micro-optic method for singlet oxygen generation and sensitizer drug delivery, which include i) synthesis and evaluation of a first generation device for drug delivery from native and fluorinated silica probe tips, ii) synthesis of PEG conjugated sensitizers to study phototoxicity in ovarian cancer cells, and iii) synthesis and evaluation of tris-PEGylated chlorin conjugated fluorinated silica for its future integration into the device to use as a 2nd generation device. A first generation micro-optic device was developed that works by sparging O2 gas and light generating cytotoxic singlet oxygen that cleaves the covalently attached drug (sensitizer) …