Biomedical Engineering and Bioengineering Commons^™

Mechanical Properties Of Nanoparticles In The Drug Delivery Kinetics, Kaivon Assani, Amy Neidhard-Doll, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Nanoparticle formulation is a recently developed drug delivery technology with enhanced targeting potential. Nanoparticles encapsulate the drug of choice and delivers it to the target via a targeting molecules (ex. antigen) located on the nanoparticle surface. Nanoparticles can even be targeted to deeply penetrating tissue and can be modeled to deliver drugs through the blood brain barrier. These advancements are providing better disease targeting such as to cancer and Alzheimer’s. Various polymers can be manufactured into nanoparticles. The polymers examined in this paper are polycaprolactone (PCL), poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), and poly(glycolic acid) (PGA). The purpose of this …

Nanoparticulate Carriers For Drug Delivery, Samantha Lokelani Crossen, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Drug delivery with nanoparticulate carriers is a new and upcoming research area that is making major changes within the pharmaceutical industry. Nanoparticulate carriers are discussed, particularly, engineered nanoparticulate carriers used as drug delivery systems for targeted delivery. Nanoparticulate carriers that are used for drug delivery systems include polymers, micelles, dendrimers, liposomes, ceramics, metals, and various forms of biological materials. The properties of these nanoparticulate carriers are very advantageous for targeted drug delivery and result in efficient drug accumulation at the targeted area of interest, reduced drug toxicity, reduced systemic side effects, and more efficient use of the drug overall. Nanoparticlulate …

Novel Hybrid Solar Nanophotonic Distillation Membrane With Photovoltaic Module For Co-Production Of Electricity And Water, Alejandro Espejo Sanchez, Nipun Goel, Todd Otanicar

Mechanical and Biomedical Engineering Faculty Publications and Presentations

Solar energy utilization and desalination are both critical needs for large portions of the world facing energy and water challenges. Direct contact membrane distillation is an attractive thermally driven desalination technique that can easily be integrated with solar energy. Here we propose and experimentally demonstrate for the first time a hybrid direct contact membrane desalination plus photovoltaic device. The system utilizes partially transparent photovoltaic cells to produce electricity and pass thermal energy to the nanoparticle doped membrane to produce thermal energy at the membrane surface. A custom lab-scale direct contact membrane distillation setup characterizes the membranes fabricated off-sun and on-sun. …

Nano-, Encapsulated Manganese Oxide (Nemo) Particles For Mri Enhancement In Microfluidic Tumor Models, Kasey Alexis Freshwater

Graduate Theses, Dissertations, and Problem Reports (ETD)

Breast cancer is among the deadliest cancers in women, with approximately 2.3 million new cases and 685,000 deaths reported globally in 2020 alone. Magnetic Resonance Imaging (MRI) is commonly used to diagnose, stage, and develop treatment plans for patients predisposed to breast cancer. However, current MRI-based screening of breast cancer has high false-positive rates up to 25%, leading to unnecessary invasive follow-up screening and testing. The gold-standard intravenous gadolinium (Gd)-based contrast agents (GBCAs) account for false-positive rates because they are always “ON”, providing a constant MRI signal that highlights both benign and malignant tumors. The work detailed in this thesis …

Tumor-Targeted Ph-Sensitive Manganese Oxide Nanoparticle For Enhanced Detection Of Breast Cancer Using Mri, Celia Martinez De La Torre

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the United States, approximately 287,850 new cases of invasive breast cancer will be diagnosed, and over 43,000 women will die because of it in 2022. Currently, mammography is the gold standard for breast cancer surveillance. Although this detection technique is relatively cheap and fast, it misses about 1 in 5 breast cancers in younger women with dense breast tissue, causing a delay in treatment. Compared to mammography, magnetic resonance imaging (MRI) has superior soft-tissue contrast that elucidates structural differences within soft tissue to detect more breast cancers. However, MRI still misses

NEMO particles were produced by synthesizing manganese oxide …

Nanoparticles For Targeted Drug Delivery To Cancer Stem Cells: A Review Of Recent Advances, Yavuz Nuri Ertas, Keyvan Abedi Dorcheh, Ali Akbari, Esmaiel Jabbari

Faculty Publications

Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug clearance. Antibodies and ligands targeting the unique factors that maintain the niche are utilized …

Zein And Lignin-Based Nanoparticles As Delivery Systems: Pesticide Release And Nanoparticle Health Impact On Soybean Plants, Fallon Polette Salinas Gonzalez

LSU Doctoral Dissertations

This research examined the effect of biodegradable, polymeric, lignin-based nanoparticles (LNPs, 113.8±3.4, negatively charged) and zein nanoparticles (ZNP, 141.6±3.9, positively charged) on soybean plant health. The LNPs were synthesized from lignin, covalently linked to poly(lactic-co-glycolic) acid by emulsion evaporation. ZNPs were synthesized by nanoprecipitation. Soybeans grown hydroponically were treated with three concentrations (0.02, 0.2, and 2 mg/ml) of NPs at 28 days after germination. The effect of ZNPs and LNPs on plant health was determined through analysis of root and stem length, chlorophyll concentration, dry biomass of roots and stem, as well as carbon, nitrogen, and micronutrient absorption after 1, …

Ionizable Lipid Nanoparticles For In Utero Mrna Delivery., Rachel S. Riley, Meghana V Kashyap, Margaret M Billingsley, Brandon White, Mohamad-Gabriel Alameh, Sourav K Bose, Philip W Zoltick, Hiaying Li, Rui Zhang, Andrew Y Cheng, Drew Weissman, William H Peranteau, Michael J Mitchell

Henry M. Rowan College of Engineering Departmental Research

Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)-mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, …

Nanoscale Material Interaction With Multicellular 3d Cancer Culture, Emilie Darrigues

Theses and Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer, it is difficult to diagnose, often recurs, has high resistance to chemotherapies, and can be marked by advanced metastatic stages. There is an urgent need to fill the knowledge on nanoparticle penetration, diffusion, and cellular interaction in the context of adaptive PDAC tumor microenvironment to allow the development of new imaging and therapeutic supports. Traditionally, cancer-treating nanoparticles have been engineered and tested on 2D cell cultures, but several studies indicate that this in vitro model does not mimic tumor features closely enough. In contrast, 3D culture models offer …

Point-Of-Care Devices For Therapeutic, Medical And Environmental Applications, Alisha Prasad

LSU Doctoral Dissertations

Point-of-care testing (POCT) or Point-of-use (POU) devices or technologies are defined as testing aids that are capable for onsite use or testing. The key advantages of POCT are low sample volume, quick onsite diagnosis, high accuracy, and cost-effectiveness. POCT has the potential and the benefits to facilitate better health care management by rapid routine diagnosis and monitoring. To reach this goal, several researchers as well as the healthcare industry over a few years have conducted cutting edge research to bring science to technology by developing smart diagnostic devices capable of performing as per patient profiles and make personalized health care …

Cancer Biomarker Detection In Human Plasma By Integrating Surface Acoustic Wave And Metal-Enhanced Fluorescence, Yuqi Huang

USF Tampa Graduate Theses and Dissertations

This thesis includes data and discussion about the technique of metal-enhanced fluorescence (MEF) to lower the detection limit of carcinoembryonic antigen (CEA). The detection limit goes down to 100pg/mL level when using MEF substrate made by rapid thermally annealed silver film covered by silica, which has great promise in diagnosing certain types of cancer that uses CEA as detection biomarker, such as pancreatic cancer and colon cancer. To further address the issue of background noises from non-specifically bound proteins (NSB) in complex media, such as plasma, serum, urine and blood, MEF is integrated with surface acoustic wave (SAW) streaming in …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

Synthetic Lethality In Pediatric Brain Cancer Cells By Optimized Plga Nanoparticles And Drug Combinations, Megan Ruckman, Megan Otte, Forrest Kievit

UCARE: Research Products

Here we test drugs effectiveness to inhibit various DNA repair pathways with the purpose of sensitizing cancer cells to radiotherapy. We work on optimizing delivery of DNA repair pathway inhibiting drugs by the use of PLGA nanoparticles.

Nanoparticle Treatment To Counter Reactive Oxygen Species After Traumatic Brain Injury, Brandon Mcdonald, Forrest Kievit

UCARE: Research Products

Traumatic brain injury (TBI) is defined as damage to the brain, resulting from an external mechanical force, such as an impact to the head (Kievit et. al, 2016).There are several examples that could result in a potential TBI; such as falling with contact to the head, car accidents and even physical activities including football, wrestling, and boxing. Because of the several different scenarios that an individual could impact their head, TBI’s have become an all too common aspect of everyday life. TBI is currently the leading cause of death and disability in children and adults under the age of 45, …

Nanoparticle-Mediated Controlled Myocardial Drug Delivery: A New Treatment For Hypertrophic Cardiomyopathy, Michelle Katherine Mcgrath Copeland

Bioengineering Dissertations - Archive

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the sarcomere, resulting in overgrowth of the septum that separates the left and right ventricles. HCM can affect as many as 1/200 people, making it the most common genetic cardiomyopathy in the general population, as well as the most common cause of sudden cardiac death (SCD). In severe HCM cases, cardiothoracic surgeons perform septal myectomy to remove the excess tissue. However, many patients are poor surgical candidates and require another, less invasive treatment option. In these cases, alcohol septal ablation (ASA) is performed. With ASA, cardiologists deliver pure alcohol through a catheter …

Formulation And Validation Of Nanoparticle Controlled Delivery For Chemotherapeutic Drug Products, Shani L. Levit

Theses and Dissertations

Taxol, a formulation of paclitaxel (PTX), is one of the most widely used anticancer drugs, particularly for treating recurring ovarian carcinomas following surgery. Clinically, PTX is used in combination with other drugs such as lapatinib (LAP) to increase treatment efficacy. Delivering drug combinations with nanoparticles has the potential to improve chemotherapy outcomes. In this study, we use Flash NanoPrecipitation, a rapid, scalable process to encapsulate weakly hydrophobic drugs (logP in vitro. Encapsulating either PTX or LAP into nanoparticles increases drug potency. When PTX and LAP are co-loaded in the same nanoparticle, they have a synergistic effect that is greater than …

Extracellular Matrix Nanoparticles Effects On The Lung In Vivo, Brittaney E. Ritchie

Theses and Dissertations

Acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes diffuse alveolar damage and a loss of the extracellular matrix (ECM). This leads to pulmonary edema and lung function deterioration. Our lab has created decellularized porcine lung, electrosprayed ECM nanoparticles that have been previously shown to have pro-regenerative capabilities in vitro.

In this study, the ECM nanoparticle effects on young murine lungs were tested in vivo. An ECM nanoparticle suspension, previously used for the in vitro studies, was aerosolized intratracheally into the lungs using a microsprayer. 24 hours later, the lung mechanics, bronchoalveolar lavage fluid, and histology …

Investigation On Nanoparticle Based Combination Therapy For Targeted Cancer Treatment, Muhammad Raisul Abedin

Doctoral Dissertations

“The current treatment methods in cancer are associated with toxicity in healthy tissues, partial therapeutic response, drug resistance and finally recurrence of the disease. The cancer drugs are challenged by non-specific binding, undesired toxicity in healthy cells, low therapeutic index and finally poor therapeutic outcome. In this work, a targeted nanoscale therapeutic system Antibody Drug Nanoparticle (ADN) was engineered to selectively inhibit the breast cancer cell growth with reduced toxicity in healthy cells. The ADNs were designed by synthesizing rod shaped anoparticles using pure chemotherapeutic drug and covalently conjugating a therapeutic monoclonal antibody (mAb) on the surface of the drug …

Liver Cancer: Current And Future Trends Using Biomaterials, Sue Anne Chew, Stefania Moscato, Sachin George, Bahareh Azimi, Serena Danti

Health & Biomedical Sciences Faculty Publications

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer diagnosed and the second leading cause of death worldwide. Despite advancement in current treatments for HCC, the prognosis for this cancer is still unfavorable. This comprehensive review article focuses on all the current technology that applies biomaterials to treat and study liver cancer, thus showing the versatility of biomaterials to be used as smart tools in this complex pathologic scenario. Specifically, after introducing the liver anatomy and pathology by focusing on the available treatments for HCC, this review summarizes the current biomaterial-based approaches for systemic delivery and implantable tools …

Lung Cancer Targeted Chemotherapy Via Herceptin Based Chimeric Antigen Receptor (Car) Engineered T Cell Membrane Coated Synthetic Nanoparticles, Serkan Yaman

Bioengineering Dissertations - Archive

Cell membrane-derived nanoparticles recently caught attention due to their desirable features in drug delivery such as mimicking properties of native tissue and cells, avoiding systemic clearance, and alleviating foreign body responses. Besides nanoparticle technology, adoptive immunotherapy has emerged for its promising treatment modalities, including cancer specificity. Our long-term goal for this research is to develop a biomimetic drug carrier based on chimeric antigen receptor (CAR) transduced T cell membranes. In the study, anti-cancer drug afatinib loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) co-extruded with anti her-2 based chimeric antigen receptor (CAR) Jurkat T cell membranes. Anti her-2 CAR-T cells were produced by …

Development Of An In Vitro Tbi Models And Validation Of Nanodelivery For Restoration Of Disrupted Brain Endothelium, Edidiong I. Inyang

Bioengineering Dissertations - Archive

Blast-induced traumatic brain injury (bTBI) is a serious concern among military personnel and their families. Although the mechanisms responsible for disruption to the brain are not well understood, the development of reliable diagnosis along with effective therapeutic treatment is urgently warranted. Recent findings suggest that shockwaves produced by a blast can generate micron-size bubbles that subsequently collapse in the brain tissue. The collapse of microbubbles (referred to as microcavitation) may compromise the integrity of the blood-brain barrier (BBB). Moreover, addiction to the psycho-stimulant drugs (PSDs), e.g. cocaine and alcohol which are known to cause toxicity due to oxidative stress, can …

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 …

Obstacles To Translating The Promise Of Nanoparticles Into Viable Amyloid Disease Therapeutics, N. P. Van Der Munnik, M. A. Moss, M. J. Uline

Faculty Publications

Nanoparticles (NPs) constitute a powerful therapeutic platform with exciting prospects as potential inhibitors of amyloid-β (Aβ) aggregation, a process associated with Alzheimer's disease (AD). Researchers have synthesized and tested a large collection of NPs with disparate sizes, shapes, electrostatic properties and surface ligands that evoke a variety of responses on Aβ aggregation. In spite of a decade of research on the NP-Aβ system and many promising experimental results, NPs have failed to progress to any level of clinical trials for AD. A theoretical framework with which to approach this physical system is presented featuring two simple metrics, (1) the extent …

Stimuli-Responsive Nanoparticles For Treatment Of Lung Cancer, Roshni Iyer

Bioengineering Dissertations - Archive

Despite extensive research and progress in anti-cancer therapeutics, an effective treatment for non-small cell lung cancer (NSCLC) remains elusive, resulting in poor 5-year patient survival rate. Towards this end, we have explored a therapeutic regimen to improve the effects of local concurrent chemo-radiation-therapy (CRT), by utilizing multifunctional stimuli-responsive nanoparticles (NPs) as drug carriers. We have also utilized lung cancer targeting strategies for site-specific drug delivery, mainly antibodies against the Ephrin-transmembrane receptor kinase (EphA2), that is over-expressed mainly on lung cancer cells, to promote the targeted delivery of drugs to only cancer cells, and eventually reduce the toxicity to healthy tissues. …

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 …

Development Of Mussel Inspired Nanocomposite Adhesives For Biomedical Applications, Nikhil Pandey

Bioengineering Dissertations - Archive

Popular bioadhesives, such as fibrin, cyanoacrylate and albumin–glutaraldehyde-based materials, have been applied for clinical applications in wound healing, drug delivery, and bone and soft tissue engineering; however, their performances are limited by weak adhesion strength and rapid degradation. The long-term goal of this research is to develop a strong tissue adhering nanocomposite for tissue interfacing and wound healing applications. We begin by developing a mussel-inspired, nanocomposite–based, biodegradable tissue adhesive by blending poly (lactic-co-glycolic acid) (PLGA) or N-hydroxysuccinimide modified PLGA nanoparticles (PLGA-NHS) and polydopamine nanoparticles with mussel-inspired polymers. Adhesive strength measurement of the nanocomposites on porcine skin-muscle constructs revealed that the …

Nanoparticles For Gene Therapy And Protein Delivery To Induce Angiogenesis As An Alternative Treatment For Peripheral Arterial Disease, Linda Christellia Noukeu

Bioengineering Dissertations - Archive

Peripheral arterial disease (PAD) is defined as a slow, progressive disorder of the lower extremity arterial vessels characterized by chronic narrowing that often results in occlusion and is associated with loss of functional capacity. Although the PAD occurrence rate is increasing in the elderly population, outcomes with current treatment strategies are suboptimal. Hence, there is an urgent need to develop new technologies that overcome limitations of traditional modalities for PAD detection and therapy. In this research, nanoparticles have been developed and used as carriers for various therapeutic agents to treat PAD. In particular, via protein/gene delivery, we developed and formulated …

A Biodegradable Piezoelectric Composite Scaffold Containing Zinc Oxide For Cartilage Repair Applications, Ateka Mohd Arabi Khader

Dissertations

Osteoarthritis (OA) affects 27 million adults in the United States. OA causes degeneration of articular cartilage and subchondral bone. Articular cartilage has limited ability to regenerate and repair. Bone and cartilage tissues have known piezoelectric properties, which means they can generate electrical activity in response to mechanical deformation. Using a biomimetic approach, zinc oxide (ZnO), which has known piezoelectric properties, is fabricated into a flexible three-dimensional fibrous scaffold by embedding ZnO nanoparticles into slow degrading polycaprolactone (PCL). Zinc ions can be released from the fibrous scaffold over time, which also may be beneficial for cell function since zinc has well-known …

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, …