Biomedical Engineering and Bioengineering Commons^™

Silane Modulation Of Protein Conformation And Self-Assembly, Abul Bashar Mohammad Giasuddin

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

This research focused on development of nanoparticle- based therapeutics against amyloid fibrils. Amyloid fibrils are associated with various diseases such as Parkinson’s, Huntington’s, mad cow disease, Alzheimer’s, and cataracts. Amyloid fibrils develop when proteins change their shape from a native form to a pathogenic “misfolded” form. The misfolded proteins have the ability to recruit more native proteins into the pathogenic forms, which self-assemble into amyloid fibrils that are hallmarks of the various protein-misfolding diseases listed above. Amyloid fibrils are highly resistant to degradation, which may contribute to the symptoms of amyloid diseases. Synthetic drugs, natural compounds, and antibodies are widely …

Intravenous Administration Of Iron Oxide Nanoparticles In The Chicken Model, Huong Thi Ngoc Le

Graduate Theses and Dissertations

To be used in health care, the safety and effectiveness of nanoparticles needs to be tested in a living organism. The objective of this project was to develop the chicken as a convenient animal model to examine tissue targeting of intravenously (i.v.)-injected iron oxide (IO) nanoparticles. In Experiment 1, different doses of IO-COOH were i.v. injected into chickens; blood was collected at 0, 5, 15, 30, and 60 minutes post-injection; liver, spleen, lung, and kidney were collected after the last blood collection. For Experiment 2, IO-COOH and IO-PEG were i.v. injected into chickens; blood and the organs were collected at …

Antibody-Nanoparticle Conjugates To Enhance The Sensitivity Of Elisa-Based Detection Methods., Margaret M Billingsley, Rachel S. Riley, Emily S Day

Henry M. Rowan College of Engineering Departmental Research

Accurate antigen detection is imperative for clinicians to diagnose disease, assess treatment success, and predict patient prognosis. The most common technique used for the detection of disease-associated biomarkers is the enzyme linked immunosorbent assay (ELISA). In an ELISA, primary antibodies are incubated with biological samples containing the biomarker of interest. Then, detectible secondary antibodies conjugated with horseradish peroxidase (HRP) bind the primary antibodies. Upon addition of a color-changing substrate, the samples provide a colorimetric signal that directly correlates to the targeted biomarker concentration. While ELISAs are effective for analyzing samples with high biomarker content, they lack the sensitivity required to …

Modified Pamam Dendrimers In Tunable Drug-Delivery Systems: A Sustained-Release Dendrimer Hydrogel For Anti-Glaucoma Drugs And Surface-Engineered Macrophages As Nanoparticle Carriers For Targeted Anti-Cancer Therapy, Christopher A. Holden

Theses and Dissertations

Two specific drug-delivery applications were sought in this work using polyamidoamine (PAMAM) dendrimers. One drug-delivery system used a novel dendrimer hydrogel (DH) for sustained delivery of anti-glaucoma drugs. In this work, PAMAM G3.0 dendrimers were covalently bonded with poly(ethylene glycol) (PEG­₁₂₀₀₀) molecules which were subsequently acrylated, resulting in photocurable DH conjugates. For pharmacological studies, DH were loaded with a solution of intraocular pressure lowering drugs, brimonidine and timolol maleate, and were characterized for in vitro release and ex vivo transport and uptake. DH formulations were shown to increase the loading of drug molecules, increase transcorneal drug delivery, and …

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 …

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 …

Graphene Quantum Dots-Based Drug Delivery For Ovarian Cancer Therapy, Yiru Qin

USF Tampa Graduate Theses and Dissertations

Ovarian cancer, one of the most dreadful malignancies of the female reproductive system, poses a lethal threat to women worldwide. In this dissertation, the objective was to introduce a novel type of graphene quantum dots (GQDs) based nano-sized drug delivery systems (DDS) for ovarian cancer treatment. As a starting point, the facile synthesis method of the GQDs was established. Subsequently, the targeting ligand,folic acid (FA), was conjugated to GQDs. Next, a FDA approved chemotherapeutic drug, Doxorubicin (DOX), was loaded to form the GQDs-FA-DOX nano-conjugation as the DDS. Moreover, the uptake profile and anti-cancer effect of the GQDs-FA-DOX were validated in …

Synthesis And Characterization Of Curcumin Polymer For Application In Radiation Induced Lung Damage, Mark C. Bailey

Theses and Dissertations--Chemical and Materials Engineering

Radiotherapy is used as a primary treatment for many cancers, including lung cancer. Although radiotherapy has proven to be an effective cancer treatment, its use is heavily limited due to the peripheral toxicity to healthy tissue. In this work, the antioxidant, curcumin, was tested as a radioprotectant to reduce radiation damage to healthy cells. Curcumin has been limited in use due to its poor bioavailability. In order to avoid problems associated with free curcumin delivery, curcumin poly(beta-amino ester) (CPBAE) was synthesized.

The first study investigated the in vitro radioprotection effect of curcumin in HUVEC dosed with gamma radiation. Cells treated …

Improving Nano-Drug Delivery By Using Near-Real Time Sensing And Feedback, Pratik Adhikari

Doctoral Dissertations

Personalized medicine, seen as the solution to address the variability among the individuals, is the movement which proposes customization of medical procedures based on the need of the patient during the stages of prevention, diagnosis, treatment, and follow up. As the technology in medicine expands and newer methods of diagnosis and treatment are introduced in the clinic, real time data from the procedures is critical to assess the performance at point of care. Real time feedback, through collection of data at point of care would help make informed clinical decisions, potentially improving the efficacy of the treatment. In this dissertation, …

Ultrahigh Field Magnetic Resonance Imaging – Technical Development And Translational Applications, Judy Alper

Dissertations and Theses

Magnetic resonance imaging (MRI) may be used to provide detailed images of the human body with excellent soft tissue contrast. Alongside its current widespread clinical applications for diagnosis and treatment, MRI allows researchers to measure structure and function of different tissue types in order to advance our understanding of human biology and enable new medical applications of MRI. In particular, diseases affecting nerves and vessels, such as trigeminal neuralgia, with uncertain etiology can be studied using multiple MRI modalities so that treatment planning can we more effective and patient outcomes can be improved. Ultrahigh field MRI scanners, such as those …

Intracellular Ros Mediates Gas Plasma-Facilitated Cellular Transfection In 2d And 3d Cultures, Dehui Xu, Biqing Wang, Yujing Xu, Zeyu Chen, Qinjie Cui, Yanjie Yang, Hailan Chen, Michael G. Kong

Bioelectrics Publications

This study reports the potential of cold atmospheric plasma (CAP) as a versatile tool for delivering oligonucleotides into mammalian cells. Compared to lipofection and electroporation methods, plasma transfection showed a better uptake efficiency and less cell death in the transfection of oligonucleotides. We demonstrated that the level of extracellular aqueous reactive oxygen species (ROS) produced by gas plasma is correlated with the uptake efficiency and that this is achieved through an increase of intracellular ROS levels and the resulting increase in cell membrane permeability. This finding was supported by the use of ROS scavengers, which reduced CAP-based uptake efficiency. In …

Bioactive Poly(Beta-Amino Ester) Biomaterials For Treatment Of Infection And Oxidative Stress, Andrew L. Lakes

Theses and Dissertations--Chemical and Materials Engineering

Polymers have deep roots as drug delivery tools, and are widely used in clinical to private settings. Currently, however, numerous traditional therapies exist which may be improved through use of polymeric biomaterials. Through our work with infectious and oxidative stress disease prevention and treatment, we aimed to develop application driven, enhanced therapies utilizing new classes of polymers synthesized in-house. Applying biodegradable poly(β-amino ester) (PBAE) polymers, covalent-addition of bioactive substrates to these PBAEs avoided certain pitfalls of free-loaded and non-degradable drug delivery systems. Further, through variation of polymer ingredients and conditions, we were able to tune degradation rates, release profiles, cellular …

Synthesis And Functional Evaluation Of Peptide Modified Poly (Lactic-Co-Glycolic Acid) Nanoparticles To Inhibit Porphyromonas Gingivalis Biofilm Formation., Paridhi Kalia

Electronic Theses and Dissertations

Periodontal disease is an oral inflammatory disorder that afflicts roughly 46% of the adults in the U.S. Currently, treatment of periodontal disease involves the removal of plaque from the gingival pocket (with possible antibiotic treatment) and if necessary, gingival surgery. To our knowledge, no therapeutic approach exists that promotes host-biofilm homeostasis by limiting pathogen recolonization of the oral cavity after prophylaxis or treatment. The interaction of the pathogen Porphyromonas gingivalis with commensal streptococci is critical for initiation of periodontitis and represents a target for limiting P. gingivalis colonization of the oral cavity. Previous studies showed that a synthetic peptide …

Thermosensitive Gel Containing Cellulose Acetate Phthalate-Efavirenz Combination Nanoparticles For Prevention Of Hiv-1 Infection, Abhijit A. Date, Annemarie Shibata, Emily Mcmullen, Krista La Bruzzo, Patrick Bruck, Michael Belshan, You Zhou, Christopher J. Destache

Nebraska Center for Biotechnology: Faculty and Staff Publications

The objective of this investigation was to develop and evaluate a nano-microbicide containing a combination of cellulose acetate phthalate (HIV-1 entry inhibitor) and efavirenz (anti-HIV agent) for HIV prophylaxis. Cellulose acetate phthalate-efavirenz combination nanoparticles (CAP-EFV-NPs) were fabricated by the nanoprecipitation method and were characterized for particle size, zeta potential and encapsulation efficiency of efavirenz. CAP-EFV-NPs were incorporated into a thermosensitive gel (CAP-EFV-NP-Gel). CAP-EFV-NPs, CAP-EFV-NP-Gel and efavirenz solution were evaluated for cytotoxicity to HeLa cells and for in vitro short-term (1-day) and long-term (3-day) prophylaxis against HIV-1 infection in TZM-bl cells. CAP-EFV-NPs had size < 100 nm, negative surface charge and encapsulation efficiency of efavirenz was > 98%. CAP-EFV-NPs and CAP-EFV-NP-Gel were significantly less …

Inhalable Nanocomposites And Anticancer Agents For Cancer Therapy, Nathanael A. Stocke

Theses and Dissertations--Chemical and Materials Engineering

Cancer is designated as the leading cause of mortality worldwide and lung cancer is responsible for nearly 30% of all cancer related deaths. Over the last few decades mortality rates have only marginally increased and rates of recurrence remain high. These factors, among others, suggest the need for more innovative treatment modalities in lung cancer therapy. Targeted pulmonary delivery is well established for treating pulmonary diseases such as asthma and provides a promising platform for lung cancer therapy. Increasing local deposition of anticancer agents (ACAs) and reducing systemic exposure of these toxic moieties could lead to better therapeutic outcomes and …

Nanotechnology And Additive Manufacturing Platforms For Clinical Medicine: An Investigation Of 3d Printing Bioactive Constructs And Halloysite Nanotubes For Drug Delivery And Biomaterials, Jeffery A. Weisman

Doctoral Dissertations

Personalized medicine requires the development of new technologies for controlled or targeted drug delivery. Three-dimensional (3D) printing and additive manufacturing techniques can be used to generate customized constructs for bioactive compound delivery. Nanotechnology in the form of nanoparticles, used as a stand-alone construct or for material enhancements, can significantly improve established biomaterials such as PMMA based bone cements or enable new technology to have enhanced capabilities. Combinations of the technologies can be used in such applications as infectious disease treatments, chemotherapeutic targeted drug delivery or targeted delivery of nearly any bioactive compound.

Chemotherapeutic or antibiotic enhanced 3D printing filaments were …

Developent Of A Phospholipid Encapsulation Process For Quantum Dots To Be Used In Biologic Applications, Logan Grimes

Master's Theses

The American Cancer Society predicts that 1,665,540 people will be diagnosed with cancer, and 585,720 people will die from cancer in 2014. One of the most common types of cancer in the United States is skin cancer. Melanoma alone is predicted to account for 10,000 of the cancer related deaths in 2014. As a highly mobile and aggressive form of cancer, melanoma is difficult to fight once it has metastasized through the body. Early detection in such varieties of cancer is critical in improving survival rates in afflicted patients. Present methods of detection rely on visual examination of suspicious regions …

Combined Metal-Enhanced Fluorescence-Surface Acoustic Wave (Mef-Saw) Biosensor, Samuel Morrill

USF Tampa Graduate Theses and Dissertations

Immunofluorescence assays are capable of both detecting the amount of a protein and the location of the protein within a cell or tissue section. Unfortunately, the traditional technique is not capable of detecting concentrations on the nanoscale. Also, the technique suffers from non-specific attachment, which can cause false-positives, as well as photobleaching when detecting lower concentrations is attempted. There is also a time constraint problem since the technique can take from many hours to a few days in some cases.

In this work, metal-enhanced fluorescence (MEF) is used to lower the detection limit and reduce photobleaching. Unfortunately, MEF also increases …

Polysaccharide-Based Nanocarriers For Improved Drug Delivery, Nan Zhang

Dissertations - ALL

The field of drug delivery has provided a solution to the limited efficacy and high toxicity of many drugs. Nano-sized drug carriers are popular because their size allows for selective accumulation in the diseased area. Polysaccharides are non-toxic and biodegradable natural polymers that can serve as the basis for these nano-sized carriers. Polysialic acid (PSA) is such a polysaccharide with strong hydrophilicity that may reduce uptake by the reticuloendothelial system and prolong drug circulation. In this study, we developed PSA-based nanocarriers, specifically micelles and nanoparticles, for improved drug delivery with improved efficacy and minimized toxicity. PSA-based micelle systems were developed …

Development Of Vapor Deposited Silica Sol-Gel Particles For A Bioactive Materials System To Direct Osteoblast Behavior, Katherine Lynn Snyder

Dissertations, Master's Theses and Master's Reports - Open

Tissue engineering and regenerative medicine have emerged in an effort to generate replacement tissues capable of restoring native tissue structure and function, but because of the complexity of biologic system, this has proven to be much harder than originally anticipated. Silica based bioactive glasses are popular as biomaterials because of their ability to enhance osteogenesis and angiogenesis. Sol-gel processing methods are popular in generating these materials because it offers: 1) mild processing conditions; 2) easily controlled structure and composition; 3) the ability to incorporate biological molecules; and 4) inherent biocompatibility. The goal of this work was to develop a bioactive …

Techniques To Quantify The Size Of Protein Colloids In Amyloid Fiber Formation, Jonathan R. Anson, Chia-Hung Lu, Lingwen Cui, Xiaojing Yang, Shaohua Xu

Biomedical Engineering and Sciences Faculty Publications

A new method for the analysis of protein colloidal diameter has been developed using three existing protein concentration quantification techniques, absorption at 280 nm, colloidal gold assay, and DC protein assay. Protein colloids are formed in the process of aggregation and are thought to be intermediates in protein self-assembly and formation of amyloid fiber. Deposition of the protein fibers in tissues leads to numerous human diseases including Alzheimer’s. Lysozyme was incubated at pH 2.0, 55°C, an environment conducive to amyloid fiber formation. The protein colloids present in the supernatant of the samples after centrifugation were studied over a time course …

Nanomaterials For Photo-Based Diagnostic And Therapeutic Applications, Baohong Yuan, Jyothi Unnikrishna Menon, Khanh Vu, Parth V. Jadeja, Kytai Truong Nguyen, Pranjali P. Tambe

Bioengineering Faculty Publications - Archive

Photo-based diagnosis and treatment methods are gaining prominence due to increased spatial imaging resolution, minimally invasive modalities involved as well as localized treatment. Recently, nanoparticles (NPs) have been developed and used in photo-based therapeutic applications. While some nanomaterials have inherent photo-based imaging capabilities, others including polymeric NPs act as nanocarriers to deliver various fluorescent dyes or photosensitizers for photoimaging and therapeutic applications. These applications can vary from Magnetic Resonance Imaging (MRI) and optical imaging to photothermal therapy (PTT) and chemotherapy. Materials commonly used for development of photo-based NPs ranges from metal-based (gold, silver and silica) to polymer- based (chitosan, dextran, …

Applications Of Antioxidant And Anti-Inflammatory Polymers To Inhibit Injury And Disease, David B. Cochran

Theses and Dissertations--Chemical and Materials Engineering

There is an undeniable link between oxidative stress, inflammation, and disease. Currently, approaches using antioxidant therapies have been largely unsuccessful due to poor delivery and bioavailability. Responding to these limitations, we have developed classes of polymer and delivery systems that can overcome the challenges of antioxidant and anti-inflammatory therapy. In our initial studies, nanoparticles of poly(trolox), a polymeric form of trolox, were surface-modified with antibodies. This modification allows for specific targeting to endothelial cells, affording controllable and localized protection against oxidative stress. We have shown these targeted nanoparticles bind, internalize, and provide protection against oxidative stress generation and cytotoxicity from …

Controlled Delivery Of Tgf-Ss1 From Plga Nanoparticles, Pratik K. Vaidya

ETD Archive

Abdominal aortic aneurysms (AAAs) typically manifest as localized wall weakening and dilation of the infrarenal aorta, which grows gradually, and ultimately leads to fatal rupture. It is caused due to overexpression of proteolytic enzymes (matrix metalloproteases or MMPs) resulting into disruption of tissue structure, especially elastic matrix, which cannot be regenerated by adult vascular cells. On account of post-operative complications associated with their surgical repair, there is a critical need for developing non-surgical strategies for slowing and even regressing AAA growth. Recent studies in our laboratory have demonstrated that 1 ng/mL of transforming growth factor-β1 (TGF-β1) enhances regenerative repair by …

Targeted Multistage Delivery Of Nanoparticles To The Bone Marrow, Aman Mann

Dissertations and Theses (Open Access)

Bone marrow is a target organ site involved in multiple diseases including myeloproliferative disorders and hematologic malignancies and metastases from breast and prostate. Most of these diseases are characterized with poor quality of life, and the treatment options are only palliative due to lack of delivery mechanisms for systemically injected drugs which results in dose limitation to protect the healthy hematopoietic cells. Therefore, there is a critical need to develop effective therapeutic strategies that allow for selective delivery of therapeutic payload to the bone marrow. Nanotechnology-based drug delivery systems provide the opportunity to deliver drugs to the target tissue while …

Structure And Optical Properties Of Self-Assembled Multicomponent Plasmonic Nanogels, Tao Cong, Satvik N. Wani, Peter Anthony Paynter, Radhakrishna Sureshkumar

Biomedical and Chemical Engineering - All Scholarship

Multicomponent plasmonic nanogels (PNGs) capable of broadband absorption of light in the 400-700 nm wavelength range were synthesized by the self-assembly of metal nanoparticles with wormlike surfactant micelles. Small angle x-ray scattering and rheological experiments suggest that the nanoparticles bridge micelle fragments to aid the formation a stable gel phase with exceptional color uniformity. Their optical absorbance could be robustly tuned by changing the nanoparticle type (Au/Ag), size, shape, and/or concentration. The PNGs have relatively low viscosity and are thermoreversible. Potential applications to the manufacturing of coatings and interfaces for solar energy harvesting and reconfigurable optical devices can be envisioned.

Application Of Nanotechnology For Targeted Delivery Of Antibacterial Enzymes And For Enzyme-Based Coatings On Medical Devices And Implants, Rohan Satishkumar

All Dissertations

The frequency of S. aureus infection and subsequent biofilm formation associated with vascular catheterization has been increasing in recent years and often begins as a local colonization at the site of the catheter insertion. Antimicrobial enzymes and peptides, which are effective against a broad range of pathogens and low rates of resistance, have attracted attention as promising alternative candidates in treatment of infections caused by antibiotic resistant bacteria. The use of nanoparticles as carriers for enzymes, in addition to their size, charge, high surface area per volume etc. offers targeted delivery of enzymes to pathogenic bacteria. We proposed to use …

Targeted Nanoparticles For Cancer Therapy: Promises And Challenge, Kytai Truong Nguyen

Bioengineering Faculty Publications - Archive

No abstract provided.