Medicine and Health Sciences Commons^™

Design Of A Modified Stewart Platform Manipulator For Misalignment Correction, Adekunle Ayoko

Master of Technology Management Plan II Graduate Projects

This thesis work is about the design of a modified Stewart platform manipulator for misalignment correction. The common version of the Stewart platform uses six actuators. The traditional Stewart platform of this kind has a moving top plate and a fixed base plate. However, in this research, the modified design of the traditional Stewart platform is studied. It is designed to be an easy connect-disconnect platform that can wrap around different structures with different cross sections and symmetrically designed. It is able to adjust position easily by using four identical but independent linear actuators populated evenly in two parts fastened …

Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley

Doctoral Dissertations

Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying …

Mechanism Of Interaction Of Peptide Modified Nanoparticles With Porphyromonas Gingivalis., Ankita Jain

Electronic Theses and Dissertations

Studies suggest that P. gingivalis functions as a keystone pathogen and interacts with primary colonizers in the supragingival biofilm such as S. gordonii. This interaction contributes to the initial colonization of the oral cavity by P. gingivalis and thus represents a potential target for therapeutic intervention. We have identified a peptide (BAR) derived from the streptococcal SspB protein that functions to inhibit P. gingivalis adherence to S. gordonii. In addition, we showed that nanoparticles (NPs) functionalized with BAR inhibit this interaction more potently than free soluble peptide, possibly by promoting interaction with P. gingivalis at higher valency than …

Photothermal Therapy Improves The Efficacy Of A Mek Inhibitor In Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors., Elizabeth E. Sweeney, Rachel A. Burga, Chaoyang Li, Yuan Zhu, Rohan Fernandes

Pediatrics Faculty Publications

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors with low survival rates and the leading cause of death in neurofibromatosis type 1 (NF1) patients under 40 years old. Surgical resection is the standard of care for MPNSTs, but is often incomplete and can generate loss of function, necessitating the development of novel treatment methods for this patient population. Here, we describe a novel combination therapy comprising MEK inhibition and nanoparticle-based photothermal therapy (PTT) for MPNSTs. MEK inhibitors block activity driven by Ras, an oncogene constitutively activated in NF1-associated MPNSTs, while PTT serves as a minimally invasive method to ablate …

Use Of A Modified Greenscreen Tool To Conduct A Screening-Level Comparative Hazard Assessment Of Conventional Silver And Two Forms Of Nanosilver., Jennifer Sass, Lauren Heine, Nina Hwang

Environmental and Occupational Health Faculty Publications

BACKGROUND: Increased concern for potential health and environmental impacts of chemicals, including nanomaterials, in consumer products is driving demand for greater transparency regarding potential risks. Chemical hazard assessment is a powerful tool to inform product design, development and procurement and has been integrated into alternative assessment frameworks. The extent to which assessment methods originally designed for conventionally-sized materials can be used for nanomaterials, which have size-dependent physical and chemical properties, have not been well established. We contracted with a certified GreenScreen profiler to conduct three GreenScreen hazard assessments, for conventional silver and two forms of nanosilver. The contractor summarized publicly …

Targeted And Controlled Anticancer Drug Delivery And Release With Magnetoelectric Nanoparticles, Alexandra Rodzinski

FIU Electronic Theses and Dissertations

A major challenge of cancer treatment is successful discrimination of cancer cells from healthy cells. Nanotechnology offers multiple venues for efficient cancer targeting. Magnetoelectric nanoparticles (MENs) are a novel, multifaceted, physics-based cancer treatment platform that enables high specificity cancer targeting and externally controlled loaded drug release. The unique magnetoelectric coupling of MENs allows them to convert externally applied magnetic fields into intrinsic electric signals, which allows MENs to both be drawn magnetically towards the cancer site and to electrically interface with cancer cells. Once internalized, the MEN payload release can be externally triggered with a magnetic field. MENs uniquely allow …

Design Of Drug Nano-Carriers For Study Of Multidrug Resistance In Single Live Cells, Pavan Kumar Cherukuri

Chemistry & Biochemistry Theses & Dissertations

Multidrug resistance (MDR) exists in both prokaryotic and eukaryotic cells. MDR is responsible for ineffective treatment of a wide range of diseases, such as infections and cancer. The ATP-binding cassette (ABC) membrane transporters (efflux pumps) are one of the largest and most diverse super-families of membrane proteins found in all living organisms, ranging from bacteria to humans. All ABC transporters share a common structure of four core domains; two transmembrane domains (TMD) with variable sequence and topology and two nucleotide-binding domains (NBD) with conserved sequences. Conventional methods for the study of the efflux functions are radioactively labeled substrates and fluorescent …

Selective Anticancer Activity Of Hydroxyapatite/Chitosan-Poly(D,L)-Lactide-Co-Glycolide Particles Loaded With An Androstane-Based Cancer Inhibitor, Nenad Ignjatović, Katarina M. Penov-Gaši, Victoria M. Wu, Jovana J. Ajduković, Vesna V. Kojić, Dana Vasiljević-Radović, Maja Kuzmanović, Vuk Uskoković, Dragab Uskoković

Pharmacy Faculty Articles and Research

In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. ¹H NMR and ¹³C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the …

Long-Acting Antiretroviral Nanoformulation Development And Subcellular Trafficking, Dongwei Guo

Theses & Dissertations

The introduction of nanoformulated antiretroviral therapeutic regimens is a promising alternative to standard once a day oral treatment of HIV infection. Our lab has pioneered this effort and was successful in harnessing mononuclear phagocytes (monocytes, dendritic cells and macrophages) as nanoformulated drug carriers. The approach was developed as Trojan horses for drug transport, delivery and distribution to sites of viral replication in order to facilitate microbial elimination in HIV sanctuaries. However, the remaining challenges for current antiretroviral nanoformulations include to formulate a broad range of hydrophilic short-acting drugs, and to elucidate the mechanism of sequestered nanoparticles in macrophages at the …

Ginseng Polysaccharides Nanoparticles - Synthesis, Characterization, And Biological Activity, Kazi Farida Akhter

Electronic Thesis and Dissertation Repository

North American (NA) ginseng is a widely used medicinal plant. Polysaccharides (PS), the major medicinal fractions derived from NA ginseng root, have been shown several biological activities including anti-carcinogenic, anti-aging, immunostimulatory and antioxidant activity. This work focused on nanoprocessing of ginseng PS for enhancing their immunostimulation. Herein, we have developed a novel microfluidic approach to synthesize ginseng PS nanoparticles (NPs) from NA ginseng root. The microfluidics was found to provide unimodal PS spheres down to 20 nm with very narrow particle size distributions. In addition, the immunostimulating effect was investigated on Murine macrophage cell lines, with the results revealing an …

Controlled Delivery Of Angiogenic And Arteriogenic Growth Factors From Biodegradable Poly(Ester Amide) Electrospun Fibers For Therapeutic Angiogenesis, Somiraa S. Said

Electronic Thesis and Dissertation Repository

Therapeutic angiogenesis relies on the delivery of exogenous growth factors to stimulate neovessel formation. However, systemic administration of angiogenic factors results in rapid clearance from the site of interest due to their short biological half-life. In this work, we are reporting controlled delivery of a ‘cocktail’ of growth factors, an angiogenic factor −fibroblast growth factor-2 (FGF2), and an arteriogenic factor −fibroblast growth factor-9 (FGF9), from biodegradable poly(ester amide) (PEA) electrospun fibers towards targeting neovascular formation and maturation. FGF2 and FGF9 were dual loaded into PEA fibers using a mixed blend and emulsion electrospinning technique. Matrigel tube formation and Boyden chamber …

Gold Nanostars For Efficient In Vitro And In Vivo Real-Time Sers Detection And Drug Delivery Via Plasmonic-Tunable Raman/Ftir Imaging, Furong Tian, Joao Conde, Chenchen Bao, Yunsheng Chen, James Curtin, Daxiang Cui

Articles

The application of plasmonic-enhanced Raman imaging of cancer cells and drug delivery is gaining momentum. Here, we propose a new theranostic strategy based on an efficient plasmonic-tunable Raman/Fourier transform infrared (FTIR) spectroscopy imaging, to simultaneously evaluate the anticancer drug scattering cellular imaging and the Raman scattering molecular vibration signals in living cells. This technique allows to monitoring the drug release throughout the cell cycle and in vivo biodistribution and biocompatibility with low dose drug therapy (200 µg/mL) and low toxicity effect. This system can directly track in real-time the delivery and release of an anticancer drug (mitoxantrone, MTX) from gold …

Rnai Nanotechnology: A Platform For Sirna Screening And Cancer Gene Therapy, Mayurbhai Ravikant Patel

Seton Hall University Dissertations and Theses (ETDs)

Over the past two decades, advances in RNA structural biology have improved our understanding of the structures and folding properties of naturally occurring RNAs. RNA sequences and structures participate in many specific biological functions, such as those performed by messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), micro RNA (miRNA), short-interfering RNA (siRNA), small nuclear RNA (snRNA) and many others. The noncoding RNAs, such as siRNA, do not express proteins but have been utilized in a wide range of applications, including RNA interference (RNAi) and the regulation of mRNA expression. These important biological functions have been implemented in gene …

Developing Hyperpolarized Silicon Particles For In Vivo Mri Targeting Of Ovarian Cancer, Nicholas Whiting, Jingzhe Hu, Niki M. Zacharias, Ganesh L. R. Lokesh, David E. Volk, David G. Menter, Rajesha Rupaimoole, Rebecca Previs, Anil K. Sood, Pratip Bhattacharya

Nicholas Whiting

Nanobubbles Provide Theranostic Relief To Cancer Hypoxia, Christopher M. Long, Pushpak N. Bhandari, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hypoxia is a common motif among tumors, contributing to metastasis, angiogenesis, cellular epigenetic abnormality, and resistance to cancer therapy. Hypoxia also plays a pivotal role in oncological studies, where it can be used as a principal target for new anti-cancer therapeutic methods. Oxygen nanobubbles were designed in an effort to target the hypoxic tumor regions, thus interrupting the hypoxia-inducible factor-1α (HIF-1α) regulatory pathway and inhibiting tumor progression. At less than 100nm, oxygen nanobubbles act as a vehicle for site-specific oxygen delivery, while also serving as an ultrasound contrast agent for advanced imaging purposes. Through in vitro and in vivo studies, …

Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics, Matthew L. Capek, Ross Verheul, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

The development of novel and efficient mixing methods is important for optimizing the efficiency of many biological and chemical processes. Tuning the physical and performance properties of nucleic acid-based nanoparticles is one such example known to be strongly affected by mixing efficiency. The characteristics of DNA nanoparticles (such as size, polydispersity, ζ-potential, and gel shift) are important to ensure their therapeutic potency, and new methods to optimize these characteristics are of significant importance to achieve the highest efficacy. In the present study, a simple segmented flow microfluidics system has been developed to augment mixing of pDNA/bPEI nanoparticles. This DNA and …

Mechanical Reliability Of Implantable Polyimide-Based Magnetic Microactuators For Biofouling Removal, Christian G. Figueroa-Espada, Qi Yang, Hyowon Lee

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hydrocephalus is a neurological disorder that typically requires a long-term implantation of a shunt system to manage its symptoms. These shunt systems are notorious for their extremely high failure rate. More than 40% of all implanted shunt systems fail within the first year of implantation. On average, 85% of all hydrocephalus patients with shunt systems undergo at least two shunt-revision surgeries within 10 years of implantation. A large portion of this high failure rate can be attributed to biofouling-related obstructions and infections. Previously, we developed flexible polyimide-based magnetic microactuators to remove obstructions formed on hydrocephalus shunts. To test the long-term …

Design And Development Of A Plasmid Vector For Protein Expression And Purification, Mahima Grover, Craig Sweet, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

Production and isolation of proteins are difficult, costly and time-consuming processes. The aim of this project is for the development of plasmids, which allow for streamlined production and isolation of proteins. To allow for modular insertion of varying segments of DNA we are using ‘recursive directional ligation by plasmid reconstruction’. This technique uses type II restriction endonucleases, which cut downstream from their recognition site allowing multiple insertions without losing a restriction site. Using this process, we can ligate multiple DNA sequences together and express them to be able to construct a scar less fusion protein. In order to accomplish this, …

Alternative Methods For The Treatment Of Chemo-Resistant Cancers, Kaitlyn Wong

Doctoral Dissertations

Great strides have been made in cancer therapy in the past century, yet it remains one of the leading causes of death in the United States today. This work aimed to shed light on novel methods to treat a variety of aggressive and often chemo-resistant cancers both in vitro and in vivo. The first aim of this work was to evaluate the therapeutic efficacy of poly(methacryloyloxyethyl phosphorylcholine) (polyMPC) prodrugs compared to standard chemotherapeutic agents. Conjugation of polyMPC to drugs such as doxorubicin (Dox) can result in its improved solubility, prolonged half-life and therapeutic efficacy. PolyMPC and polyMPC-Dox (at a …

Design Of Nanoparticle-Based Carriers For Targeted Drug Delivery, Xiaojiao Yu, Ian Trase, Muqing Ren, Kayla Duval, Xing Guo, Zi Chen

Dartmouth Scholarship

Nanoparticles have shown promise as both drug delivery vehicles and direct antitumor systems, but they must be properly designed in order to maximize efficacy. Computational modeling is often used both to design new nanoparticles and to better understand existing ones. Modeled processes include the release of drugs at the tumor site and the physical interaction between the nanoparticle and cancer cells. In this paper, we provide an overview of three different targeted drug delivery methods (passive targeting, active targeting, and physical targeting) and compare methods of action, advantages, limitations, and the current stages of research. For the most commonly used …

Hydrothermally Processed 1d Hydroxyapatite: Mechanism Of Formation And Biocompatibility Studies, Zoran Stojanović, Nenad Ignjatović, Victoria M. Wu, Vojca Žunič, Ljiljana Veselinović, Srečo D. Škapin, Miroslav Miljković, Vuk Uskoković, Dragab Uskoković

Pharmacy Faculty Articles and Research

Recent developments in bone tissue engineering have led to an increased interest in one-dimensional (1D) hydroxyapatite (HA) nano- and micro-structures such as wires, ribbons and tubes. They have been proposed for use as cell substrates, reinforcing phases in composites and carriers for biologically active substances. Here we demonstrate the synthesis of 1D HA structures using an optimized, urea-assisted, high-yield hydrothermal batch process. The one-pot process, yielding HA structures composed of bundles of ribbons and wires, was typified by the simultaneous occurrence of a multitude of intermediate reactions, failing to meet the uniformity criteria over particle morphology and size. To overcome …

Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review …

Gene Delivery Using Calcium Phosphate Nanoparticles: Optimization Of The Transfection Process And The Effects Of Citrate And Poly(L-Lysine) As Additives, Mohammed A. Khan, Victoria M. Wu, Shreya Ghosh, Vuk Uskoković

Pharmacy Faculty Articles and Research

Despite the long history of nanoparticulate calcium phosphate (CaP) as a non-viral transfection agent, there has been limited success in attempts to optimize its properties for transfection comparable in efficiency to that of viral vectors. Here we focus on the optimization of: (a) CaP nanoparticle precipitation conditions, predominantly supersaturation and Ca/P molar ratios; (b) transfection conditions, mainly the concentrations of the carrier and plasmid DNA; (c) the presence of surface additives, including citrate anion and cationic poly(l-lysine) (PLL). CaP nanoparticles significantly improved transfection with plasmid DNA encoding enhanced green fluorescent protein (eGFP) in pre-osteoblastic MC3T3-E1 cells compared to a commercial …

2016-01-A3dsrinp-Csc-Sta-Cmb-522-Bps-542, Raymond Pulver, Neal Buxton, Xiaodong Wang, John Lucci, Jean Yves Hervé, Lenore Martin

Bioinformatics Software Design Projects

Cholesterol is carried and transported through bloodstream by lipoproteins. There are two types of lipoproteins: low density lipoprotein, or LDL, and high density lipoprotein, or HDL. LDL cholesterol is considered “bad” cholesterol because it can form plaque and hard deposit leading to arteries clog and make them less flexible. Heart attack or stroke will happen if the hard deposit blocks a narrowed artery. HDL cholesterol helps to remove LDL from the artery back to the liver.

Traditionally, particle counts of LDL and HDL plays an important role to understanding and prediction of heart disease risk. But recently research suggested that …

Block Copolymer Based Magnetic Nanoclusters For Cancer-Theranostics: Synthesis, Characterization And In Vitro Evaluation, Hemant M. Vishwasrao

Theses & Dissertations

“There is plenty of room at the bottom”. In this visionary lecture in 1959 Prof. Richard Feynman spoke of the interesting ramifications of working with matter at the atomic scale. Since then, scientists have worked relentlessly towards realizing his vision. The influence of nanobiotechnology on material science and polymer chemistry has given rise to a new field called ‘theranostics’, combining drug delivery and diagnostics within the same nanostructures, thereby enabling simultaneous diagnosis, targeted drug delivery and continued therapy monitoring. Iron oxide nanoparticles (MNPs) are one such class of MRI contrast agents that can be converted into theranostic nanomedicines for cancer …

Customization Of Titanate Nanofiber Bioscaffolds, Jared Hopkins

Biomedical Engineering Undergraduate Honors Theses

In the field of orthopedic devices implant loosening is a major issue resulting in the majority of device failures. These failures result in the need for costly secondary procedures. To reduce device loosening an improved method of tissue anchoring is required. A previously studied titanate nanofiber bioscaffold has been shown to be safely implantable and to contribute to the differentiation of mesenchymal stem cells to osteocytes. Through the customization of both physical and chemical characteristics this titanate nanofiber bioscaffold was fabricated as a potential means to enhance tissue anchoring for use with orthopedic devices. This customization was enabled by acoustic …

An Investigation Into Formulation And Therapeutic Effectiveness Of Nanoparticle Drug Delivery For Select Pharmaceutical Agents, Dustin Cooper

Electronic Theses and Dissertations

Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug delivery systems. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Furthermore, polymer based, biodegradable nanodelivery has become increasing popular in the field of NP formulation because of their high degree of compatibility and low rate of toxicity. Due to their popularity, commercially available polymers such as poly lactic acid (PLA), poly glycolic acid (PGA) and polylactic-co-glycolic acid (PLGA) are commonly used in the development and design of new nano based delivery …

Synthesis And Characterization Of Nanoparticle-Coupled Proteins In Human Serum Albumin, Kyle M. Mahoney

Honors College Theses

Recently, cancer has become an ever-growing issue and has led to many researchers attempt to unravel the mystery of the disease. This research has led to a promising field of treatment: nanotechnology-coupled pharmaceuticals. Nanoparticles act as a whole unit when in conjugation with other molecules and add to the carrier molecule, most often proteins, benefits the nanoparticles themselves possess. One such carrier protein that can be conjugated with nanoparticles is Human Serum Albumin (HSA). Albumin is of interest in cancer research for two reasons: it is native to the human vasculature so it does not elicit immunological reactions, and it …

Gold Nanoprisms As A Hybrid In Vivo Cancer Heranostic Platform For In Situ Photoacoustic Imaging, Angiography, And Localized Hyperthermia, Chenchen Bao, Joao Conde, Fei Pan, Chao Li, Chunlei Zhang, Furong Tian, Shujing Liang, Jesus M. De La Fuente, Daxiang Cui

Articles

The development of high-resolution nanosized photoacoustic contrast agents is an exciting yet challenging technological advance. Herein, antibody (breast cancer-associated antigen 1 (Brcaa1) monoclonal antibody)- and peptide (RGD)- functionalized gold nanoprisms (AuNprs) were used as a combinatorial methodology for in situ photoacoustic imaging, angiography, and localized hyperthermia using orthotopic and subcutaneous murine gastric carcinoma models. RGD-conjugated PEGylated AuNprs are available for tumor angiography, and Brcaa1 monoclonal antibody-conjugated PEGylated AuNprs are used for targeting and for in situ imaging of gastric carcinoma in orthotopic tumor models. In situ photoacoustic imaging allowed for anatomical and functional imaging at the tumor site. In vivo …

Micronutrient Foliar Analysis And Supplementation In Nutrient Management For High Yield Maize (Zea Mays L.), Zachary P. Stewart

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

Micronutrient supplementation in maize production is of growing interest to producers and agronomists as means to further increase yield as other crop needs are increasingly met. Plant tissue and soil sampling for micronutrient concentrations have been used to determine likely responses to micronutrient supplementation. Nebraska soils are generally micronutrient sufficient and usually do not have soil or plant tissue micronutrient concentrations below critical levels, however, during precise periods where specific micronutrients are in greatest need due to physiological demands, there may be opportunity for micronutrient supplementation to increase grain yield. The compiled chapters indicate that in most scenarios in Nebraska, …