Biomedical Engineering and Bioengineering Commons^™

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 …

Cell Imaging And Data Analysis For Biomaterial-Mammalian Co-Cultures, Jefferson Pontsler

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Microscopic bioimaging is a useful approach to study cell-biomaterial interactions which are vital to the biomedical application of biomaterials. Through microscopic imaging, numerous cellular responses, such as proliferation, uptake, and death, can be recorded, characterized and analyzed.

In this thesis, I first provided basic introductions to the imaging techniques and analysis tools, especially those that are highly relevant to the studies of biomaterials and cell interactions. I also detailed the adaptation of these techniques and tools in the application of two specific research projects in biomaterials, with special focuses on the imaging and analysis.

The first project assessed the subtle …

Optical And X-Ray Technology Synergies Enabling Diagnostic And Therapeutic Applications In Medicine, Brian W. Pogue, Brian C. Wilson

Dartmouth Scholarship

X-ray and optical technologies are the two central pillars for human imaging and therapy. The strengths of x-rays are deep tissue penetration, effective cytotoxicity, and the ability to image with robust projection and computed-tomography methods. The major limitations of x-ray use are the lack of molecular specificity and the carcinogenic risk. In comparison, optical interactions with tissue are strongly scatter dominated, leading to limited tissue penetration, making imaging and therapy largely restricted to superficial or endoscopically directed tissues. However, optical photon energies are comparable with molecular energy levels, thereby providing the strength of intrinsic molecular specificity. Additionally, optical technologies are …

Multi-Beam Scan Analysis With A Clinical Linac For High Resolution Cherenkov-Excited Molecular Luminescence Imaging In Tissue., Mengyu Jeremy Jia, Peter Bruza, Lesley A. Jarvis, David J. Gladstone, Brian W. Pogue

Dartmouth Scholarship

Cherenkov-excited luminescence scanned imaging (CELSI) is achieved with external beam radiotherapy to map out molecular luminescence intensity or lifetime in tissue. Just as in fluorescence microscopy, the choice of excitation geometry can affect the imaging time, spatial resolution and contrast recovered. In this study, the use of spatially patterned illumination was systematically studied comparing scan shapes, starting with line scan and block patterns and increasing from single beams to multiple parallel beams and then to clinically used treatment plans for radiation therapy. The image recovery was improved by a spatial-temporal modulation-demodulation method, which used the ability to capture simultaneous images …

Plga-Modified Nanoparticles For The Treatment Of Hypo-Vascularized Hpv-Related Cervical Cancers., Lee B. Sims

Electronic Theses and Dissertations

A major challenge associated with delivery of active agents in the female reproductive tract (FRT) is the ability of agents to efficiently diffuse through the cervicovaginal mucosa (CVM) and reach the underlying sub-epithelial immune cell layer and vasculature. A variety of drug delivery vehicles have been employed to improve the delivery of agents across the CVM and offer the capability to increase the longevity and retention of active agents to treat infections of the female reproductive tract. Nanoparticles (NPs) have been shown to improve retention, diffusion, and cell-specific targeting via specific surface modifications, relative to other delivery platforms. In particular, …

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 …

The Design, Fabrication, And Characterization Of Nanoparticle-Protein Interactions For Theranostic Applications, Wai Hei Tse

Electronic Thesis and Dissertation Repository

Theranostics, a combination of therapeutics and diagnostics, spans a spectrum of research areas to provide new opportunities in developing new healthcare technologies and medicine at affordable prices. Through employing a personalized medicine approach, biotechnology can be tailored to the needs of an individual. Applications of theranostics include drug delivery carriers capable of sustained drug release and targeted delivery, biosensors with high sensitivity and selectivity, and diagnostic relevant entities that can be incorporated into the former technologies. Nanotechnology provides a suitable foundation for theranostics to build upon due to material-based properties; magnetism, biocompatibility, and quantum effects to name a few. Purpose …

Crafting Nanostructured Neural Interfaces With Hydrogel Particles, Emily Ann Morin

Doctoral Dissertations

Central nervous system neural device functionality hinges on effective communication with surrounding neurons. This depends on both the permissiveness of the device material to promote neuron integration and the ability of the device to avoid a chronic inflammatory response. Here, a facile approach has been developed exploring the multiple functionalities of hydrogel particles to provide cues to impart neural integration for such materials. Three distinct, yet interconnected tasks were undertaken: investigating hydrogel particle-modified substrate neuron integration and central nervous system inflammatory response, investigating guided hydrogel particle adsorption, and investigating hydrogel particles as local reservoirs for counteracting adverse effects from oxidative …

Development Of Spectroscopic Methods For Dynamic Cellular Level Study Of Biochemical Kinetics And Disease Progression, Anna M. Sitarski

Electronic Theses and Dissertations

One of the current fundamental objectives in biomedical research is understanding molecular and cellular mechanisms of disease progression. Recent work in genetics support the stochastic nature of disease progression on the single cell level. For example, recent work has demonstrated that cancer as a disease state is reached after the accumulation of damages that result in genetic errors. Other diseases like Huntingtons, Parkinsons, Alzheimers, cardiovascular disease are developed over time and their cellular mechanisms of disease transition are largely unknown. Modern techniques of disease characterization are perturbative, invasive and fully destructive to biological samples. Many methods need a probe or …

The Effect Of Hyperthermia On Doxorubicin Therapy And Nanoparticle Penetration In Multicellular Ovarian Cancer Spheroids, Abhignyan Nagesetti

FIU Electronic Theses and Dissertations

The efficient treatment of cancer with chemotherapy is challenged by the limited penetration of drugs into the tumor. Nanoparticles (10 – 100 nanometers) have emerged as a logical choice to specifically deliver chemotherapeutics to tumors, however, their transport into the tumor is also impeded owing to their bigger size compared to free drug moieties. Currently, monolayer cell cultures, as models for drug testing, cannot recapitulate the structural and functional complexity of in-vivo tumors. Furthermore, strategies to improve drug distribution in tumor tissues are also required. In this study, we hypothesized that hyperthermia (43°C) will improve the distribution of silica nanoparticles …

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 …

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 Faculty Scholarship

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 …

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 …

Magnetism Of Magnetite Nanoparticles As Determined By Mössbauer Spectroscopy, Hien-Yoong Hah

Masters Theses

Fe₃O₄ [Magnetite] nanoparticles have magnetism that differs greatly from their bulk counterparts. Whereas bulk Fe₃O₄ is a ferrimagnet, single-domain Fe₃O₄ nanoparticles have been found to be superparamagnetic. This allows for increased magnetization of the nanoparticles compared to the bulk when in a magnetic field. For most paramagnets, magnetization requires applied fields of a few Tesla at low temperatures. This is achievable through the application of superconducting magnets. In superparamagnets, the high susceptibility of the particles allows magnetization through a Nd-Fe-B permanent magnet at room temperature. This is caused by an increased …

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 …

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 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, …

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 …

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 …

Cobalt Ferrite Nanoparticles Fabricated Via Co-Precipitation In Air: Overview Of Size Control And Magnetic Properties, Dennis Toledo

FIU Electronic Theses and Dissertations

Cobalt Ferrite has important, size-dependent magnetic properties. Consequently, an overview of particle size is important. Co-precipitation in air was the fabrication method used because it is comparatively simple and safe. The effects of three different reaction times including 1, 2, 3 hour(s) on particle size were compared. Also, the effectiveness of three different capping agents (Oleic Acid, Polyvinylpyrollidone (PVP), and Trisodium Citrate) in reducing aggregation and correspondingly particle size were examined. Using Welch’s analysis of variance (ANOVA) and the relevant post hoc tests, there was no significant difference (p=0.05) between reaction times of 1 hour and 2 hours, but there …

Effect Of Ion Concentration On Mechanosynthesis Of Carbonated Chlorapatite Nanopowders

Faculty of Engineering University of Malaya

Carbonated chlorapatite nanopowders (n-CCAp) with different degrees of substitution were successfully synthesized by the one-step mechanochemical process. Results demonstrated that the formation of n-CCAp was influenced strongly by the carbonate content (x). From X-ray analysis, crystallite size, crystallinity degree, and unit cell volume of n-CCAp decreased significantly as carbonate content (x) increased from 0 to 2. Conversely, the lattice strain and the volume fraction of grain boundaries grew considerably. Microscopic analysis showed the average particle size of the synthesized powders was 15 +/- 10 nm. The influence of carbonate concentration on mechanosynthesis of pure n-CCAp utilizing a facile solid-state process …

Effect Of High-Energy Ball Milling On The Formation And Micro Structural Features Of Carbonated Chlorapatite Nanopowders

Faculty of Engineering University of Malaya

Carbonated chlorapatite nanopowders (n-CCAp) were synthesized by mechanochemical process from calcite (CaCO3), phosphorus pentoxide (P2O5), and calcium chloride (CaCl2) as raw materials. Results demonstrated that the formation of n-CCAp was influenced strongly by the milling time. At the beginning of milling (up to 15 min), CaCO3 and CaCl2 were the dominant phases, while P2O5 disappeared entirely due to its very high deliquescent nature. With increasing the milling time to 600 min, the progressive mechanochemical reaction was completed which resulted in the formation of nanostructured carbonated chlorapatite. According to the X-ray diffraction data, crystallite size of the product decreased from 24 …

Physical Properties Of Iron Oxide Nanoparticles, Nicklaus Carter

Honors College

Magnetic Resonance Imaging (MRI) relies heavily on contrast agents such that diagnosis of various diseases can be made with increased confidence. Current contrast agents for MRI depend on various chelated molecules composed of a toxic gadolinium ion, Gd³⁺. In 2006, a discovery was made connecting Nephrogenic Systemic Fibrosis (NSF) and these gadolinium based contrast agents (GBCAs). The connection between life threatening NSF and GBCAs stems from patients with pre-existing kidney malfunctions. It has been proposed that an alternative agent such as iron oxide nanoparticles (IONPs) be investigated. These IONPs theoretically will have similar responses in efficiency of improving …

Nanoparticles For Stem-Cell Engineering, Esmaiel Jabbari

Esmaiel Jabbari

No abstract provided.

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 …

Poly(Ester Amide) And Poly(Ethyl Glyoxylate) Nanoparticles For Controlled Drug Release, Amira Mohamed Moustafa

Electronic Thesis and Dissertation Repository

The objective of this research was to develop polymeric nanoparticles (NPs) having improved drug release properties for drug delivery. Poly(ester amide)s (PEAs) are promising biodegradable polymers. PEA NPs were prepared via emulsification-evaporation and salting-out methods and optimized through by varying different processing parameters. Polymer-model drug conjugates based on PEAs containing L-aspartic acid and rhodamine B were synthesized and used for NP preparation. Release behavior was studied and compared to a control system with physically encapsulated rhodamine B. It was shown that the release of rhodamine B from the covalent system did not show the burst effect and exhibited a slower …