Nanotechnology Commons^™

Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim

Theses & Dissertations

The introduction of highly active antiretroviral therapy led to a paradigm shift in the management of HIV/AIDS changing a disease considered “a death sentence” to “a manageable chronic disease”. Nevertheless, challenges exist for successful treatment of HIV, including patient adherence to the complex daily regimens and the inability of current formulations to target viral sanctuaries. Introduction of nanoformulated antiretroviral therapy (ART) is a promising alternative to tackle these challenges. Our laboratory has been focusing on developing long-acting (LA) nanoformulated antiretrovirals and has succeeded in developing LA integrase inhibitors. However, challenges for this approach extend to a range of short-acting hydrophilic …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Fabrication Of Polyelectrolyte Nanoparticles Through Hydrophobic Interaction, Ruginn Porce Catarata

Electronic Theses and Dissertations

Anticancer drugs like gemcitabine (GEM) are used to treat cancers such as, pancreatic ductal adenocarcinoma (PDAC). However, the use of free gemcitabine yields challenges including cytotoxicity to healthy cells and poor circulation time. By encapsulating GEM in nanoparticles these challenges can be overcome. In this study poly(acrylic acid) (PAA)-GEM nanoparticles are fabricated by coupling GEM onto PAA. The particle formation is driven by the hydrophobic interaction of GEM, which collects in the core of the nanoparticle, forming a PAA shell. The nanoparticles were optimized by studying the PAA/GEM ratio and pH during fabrication. Characteristics of the nanoparticles including size, morphology …

Development Of 3d Printed And 3d Metal-Based Micro/Nanofabricated, And Nano-Functionalized, Microelectrode Array (Mea) Biosensors For Flexible, Conformable, And In Vitro Applications, Charles Didier

Electronic Theses and Dissertations

Emerging fields such as "Organs on a Chip", disease modeling in vitro, stem cell manufacturing and wearable bioelectronics are demanding rapid development of 3D Microelectrode Arrays (MEAs) for electrical interfacing with biological constructs. The work reported in this thesis focuses on two developmental tracks: "Dynamic 3D MEAs" and metal microfabrication for 3D MEAs. In the first part of the thesis, we explore the capabilities and limitations of 3D printed microserpentines (µserpentines) and utilize these structures to develop dynamic 3D microelectrodes. Analytical modeling of µserpentines flexibility followed by integration into a flexible Kapton® package and PDMS insulation are demonstrated. These 3D …

Nutritional Transporter Mediated Drug Delivery For Cancer, Siddharth S. Kesharwani

Electronic Theses and Dissertations

Recent advancements in nanotechnology have unfolded novel opportunities in medicine, especially in targeted therapeutics and imaging for cancer. However, the majority of the existing nanotechnologies for cancer suffer from shortcomings such as (i) rapid elimination from the systemic circulation before reaching the cancer tissue. (ii) poor tumor accumulation, targeting, and penetration due to inadequate vasculature and extensive extracellular matrix in the tumor. Thus, overcoming these two limitations of nanotechnology is of considerable interests for cancer researchers. In this dissertation, we demonstrate the feasibility of glucose-modified nanoparticles (GLU-NPs) as an efficient cancer targeted-delivery system for enhancing the systemic circulation time and …

Therapeutic Delivery Technology And Its Economic Impact, Paul E. Savas Jr.

Senior Honors Theses

Therapeutic delivery technology is a current area of high interest in both university and industrial settings. These technologies are being developed in order to deliver therapeutic agents, such as genes, proteins, and drugs, to patients more efficiently. Nanoscale delivery vehicles have proven to be useful for these applications; these vehicles may either be naturally produced or chemically synthesized. The physical properties of these nanomaterials must be characterized correctly using instrumentation that evaluates their size, morphology, and potential for agglomeration. These technologies represent a high-growth economic area that fosters entrepreneurship and innovation. Because of this innovative spirit, research and economic interest …

Mechanisms And Thermodynamics Of The Influence Of Solution-State Interactions Between Hpmc And Surfactants On Mixed Adsorption Onto Model Nanoparticles, Salin Gupta Patel

Theses and Dissertations--Pharmacy

Nanoparticulate drug delivery systems (NDDS) such as nanocrystals, nanosuspensions, solid-lipid nanoparticles often formulated for the bioavailability enhancement of poorly soluble drug candidates are stabilized by a mixture of excipients including surfactants and polymers. Most literature studies have focused on the interaction of excipients with the NDDS surfaces while ignoring the interaction of excipients in solution and the extent to which the solution-state interactions influence the affinity and capacity of adsorption. Mechanisms by which excipients stabilize NDDS and how this information can be utilized by formulators a priori to make a rational selection of excipients is not known.

The goals of …

Graphene Nanoflake Uptake Mediated By Scavenger Receptors, Fatima Alnasser, Valentina Castagnola, Luca Boselli, Margarita Esquivel-Gaon, Esen Efeoglu, Jennifer Mcintyre, Hugh Byrne, Kenneth A. Dawson

Articles

The biological interactions of graphene have been extensively investigated over the last 10 years. However, very little is known about graphene interactions with the cell surface and how the graphene internalization process is driven and mediated by specific recognition sites at the interface with the cell. In this work, we propose a methodology to investigate direct molecular correlations between the biomolecular corona of graphene and specific cell receptors, showing that key protein recognition motifs, presented on the nanomaterial surface, can engage selectively with specific cell receptors. We consider the case of apolipoprotein A-I, found to be very abundant in the …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Combination Strategies For Targeted Delivery Of Nanoparticles For Cancer Therapy, Zhonglie He, Kangze Liu, Hugh Byrne, Patrick J. Cullen, Furong Tian, James Curtin

Books / book chapters

Pharmaceuticals, and more recently biopharmaceuticals, have become the mainstay for antineoplastic treatments in combination with surgical interventions and radiation therapy. In recent years, advances have been made in the development of nano-technological interventions for the treatment of cancer alone or in combination with existing therapeutic modalities. Nanotechnology used for therapeutic drug delivery and sensitization of photodynamic, sonodynamic and radiotherapy are now being tested in preclinical and clinical trials for the treatment of cancer. This article will review the current state of the art for nanotechnology therapies with an emphasis on targeted drug delivery and the observed and likely benefits when …

Combination Therapy: Parp Inhibitor Synergizes The Therapeutic Efficacy Of Doxorubicin In The Treatment Of Prostate Cancer, Momin Ansare

Electronic Theses & Dissertations

Men are most susceptible to prostate cancer in the United States. The general treatment options include surgery, hormone therapy, chemotherapy, and radiation therapy. But in recent days, the nanoformulation have shown promising applications in overcoming the drawbacks of the currently available treatment options. To complement, we tried to enhance the capability of the nanoparticle formulation by loading them with a novel drug combination for the treatment of prostate cancer. Herein, we synthesized folate conjugated iron oxide nanoparticles encapsulated with doxorubicin and olaparib for imaging and targeted treatment of prostate cancer. Both drugs are approved by FDA for clinical cancer treatment. …

Delivery Of Microrna With Cxcr4-Targeted Nanoparticles In Metastatic Cancer Treatment, Ying Xie

Theses & Dissertations

Metastasis is the main contributor to cancer-associated deaths. Inhibition of CXCR4 emerged as one promising approach in metastatic cancer therapy. MiRNAs represent a new class of therapeutics for cancer treatment through RNA interference-mediated gene silencing. Polymeric CXCR4 antagonist (PCX) is a dual-functional polycation to inhibit CXCR4 and deliver nucleic acids. This dissertation hypothesized that blockade of CXCR4 by PCX combined with delivery of miRNA cooperatively enhances metastatic cancer therapy.

In chapter 1, an overview of CXCR4 inhibition, miRNA delivery and CXCR4 targeted nanomedicine in cancer therapy is given.

Chapter 2 reports that PCX can effectively deliver miR-200c mimic and that …

Strategies Involving The Food-Derived Agent Curcumin To Eliminate Brain Cancer, Sumit Mukherjee

Dissertations, Theses, and Capstone Projects

Glioblastoma (GBM) is one of the most deadly forms of cancer with a mean 5-year survival rate of ≤5%. We have used the non-invasive strategy of long-term intranasal (IN) delivery of a glioblastoma-directed adduct of curcumin (CC), CC-CD68Ab, into the brain of murine GBM cell line GL261-implanted mice to study the therapeutic effect of CC on GBM remission. The treatment caused GBM tumor remission in 50% of GL261-implanted GBM mice. A similar rescue rate (60%) was also achieved through long-term intraperitoneal (i.p) infusion of a highly bioavailable phosphotidylcholine (PC)-encapsulated formulation of CC, Curcumin Phytosome Meriva (CCP), into the GL261-implanted GBM …

A Cancer-Targeted Gold Nanoparticle-Based Mri Contrast Agent., Nagwa El-Baz

Electronic Theses and Dissertations

In oncology, imaging plays a major role in terms of early detection and treatment of most types of cancer. Magnetic resonance imaging (MRI) is mostly used for cancer diagnosis due to its excellent contrast resolution. However, MRI for cancer diagnosis is somewhat limited by its sensitivity. In this thesis, we assessed the ability of theranostic platform consisting of gold nanoparticles functionalized with a cancer targeting aptamer; AS1411 and gadolinium chelate (Dotarem thiol derivative; Gd (III)-DO3A) as a MRI contrast agent to target malignant tumors by enhancing the MRI contrast of the detected tumor. The proposed technology is a novel injectable …

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …

Distribution And Localization Of Novel Iodine Nanoparticles In The Human Glioma 1242 Growing In The Brains Of Mice, Benjamin Billings

Honors Scholar Theses

Observing and designing the in vivo distribution and localization of therapeutic nanoparticles is an essential aspect of developing and understanding novel nanoparticle- based medical treatments. This study investigates novel PEGylated Iodine-based nanoparticles (INPs), an alternate composition to the more widely researched gold nanoparticles (AuNPs), which may help avoid adverse effects associated with AuNPs, such as potential toxicity and skin discoloration, when used in similar applications. Determining the localization of the novel INPs within murine brains containing human glioma U-1242MG cells is critical in assisting the development of radiation dose enhancement therapy for this aggressive cancer. Radiation dose enhancement utilizes the …

Investigating The Role Of Gold Nanoparticle Shape And Size In Their Toxicities To Fungi, Kangze Liu, Zhonglei He, Hugh Byrne, James Curtin, Furong Tian Technological University Dublin

Articles

Gold nanoparticles (GNPs) are increasingly being used in a wide range of applications, and such they are being released in greater quantities into the environment. Consequently, the environmental effects of GNPs, especially toxicities to living organisms, have drawn great attention. However, their toxicological characteristics still remain unclear. Fungi, as the decomposers of the ecosystem, interact directly with the environment and critically control the overall health of the biosphere. Thus, their sensitivity to GNP toxicity is particularly important. The aim of this study was to evaluate the role of GNP shape and size in their toxicities to fungi, which could help …

Nanoparticle-Mediated Therapeutic Agent Delivery For Treating Metastatic Breast Cancer—Challenges And Opportunities, Yunfei Li, Brock Humphries, Chengfeng Yang, Zhishan Wang

Toxicology and Cancer Biology Faculty Publications

Breast cancer (BC) is the second leading cause of cancer-related death in American women and more than 90% of BC-related death is caused by metastatic BC (MBC). This review stresses the limited success of traditional therapies as well as the use of nanomedicine for treating MBC. Understanding the biological barriers of MBC that nanoparticle in vivo trafficking must overcome could provide valuable new insights for translating nanomedicine from the bench side to the bedside. A view about nanomedicine applied in BC therapy has been summarized with their present status, which is gaining attention in the clinically-applied landscape. The progressions of …

Muc4 Based Immunotherapy For Pancreatic Cancer, Kasturi Banerjee

Theses & Dissertations

Pancreatic Cancer (PC) is a lethal disease claiming approximately 45000 lives in the US in 2018, and it establishes an elaborate immunosuppressive tumor microenvironment that aids in disease pathogenesis. Immunotherapy has emerged as a strategy to target tumor cells by reprogramming patient’s immune system. Challenges present in PC immunotherapy are: i) identifying a tumor-associated antigen that could be targeted, ii) identifying adjuvants that could efficiently deliver antigens, iii) eliciting robust anti-tumor responses and iv) overcoming peripheral tolerance and immunosuppression elicited by the tumor.

Firstly, we detected circulating autoantibodies to MUC4 present in PC patients and observed that IgM autoantibodies to …

Physiologically Based Pharmacokinetic Modeling Of Nanoceria Systemic Distribution In Rats Suggests Dose- And Route-Dependent Biokinetics, Ulrika Carlander, Tshepo Paulsen Moto, Anteneh Assefa Desalegn, Robert A. Yokel, Gunnar Johanson

Pharmaceutical Sciences Faculty Publications

Background: Cerium dioxide nanoparticles (nanoceria) are increasingly being used in a variety of products as catalysts, coatings, and polishing agents. Furthermore, their antioxidant properties make nanoceria potential candidates for biomedical applications. To predict and avoid toxicity, information about their biokinetics is essential. A useful tool to explore such associations between exposure and internal target dose is physiologically based pharmacokinetic (PBPK) modeling. The aim of this study was to test the appropriateness of our previously published PBPK model developed for intravenous (IV) administration when applied to various sizes of nanoceria and to exposure routes relevant for humans.

Methods: Experimental biokinetic data …

Toxicological Assessment Of Nanomaterials: The Role Of In Vitro Raman Microspectroscopic Analysis, Esen Efeoglu, Marcus Maher, Alan Casey, Hugh Byrne

Articles

The acceleration of nanomaterials research has brought about increased demands for rapid analysis of their bioactivity, in a multi-parametric fashion, to minimise the gap between potential applications and knowledge of their toxicological properties. The potential of Raman microspectroscopy for the analysis of biological systems with the aid of multivariate analysis techniques has been demonstrated. In this study, an overview of recent efforts towards establishing a ‘label-free high content nanotoxicological assessment technique’ using Raman microspectroscopy is presented. The current state of the art for cellular toxicity assessment and the potential of Raman microspectroscopy are discussed, and the spectral markers of the …

Preparation And Physical Properties Of Functional Barium Carbonate Nanostructures By A Facile Composite-Hydroxide-Mediated Route, Tauseef Shahid, Muhammad Arfan, Aurang Zeb, Tayyaba Bibi, Taj Muhammad Khan

Articles

In recent years, nanotechnology has given birth to numerous nanomaterials due to their increased use in various sectors of research and development. To produce these nanomaterials, nanotechnology further has opened several rooms for the potential novel methods. Composite-hydroxide-mediated (CHM) method is one of the recent chemical synthesis routes that have gained considerable importance in research due to their effortlessness and versatile nature, covering a broad range of nanomaterials to prepare.

Bacterial Lps At The Immune Modulating Component In Juzen-Taiho-To, Diego Montenegro

Dissertations, Theses, and Capstone Projects

Juzen-taiho-to (JTT) is an immune-boosting herbal formulation with an ideal balance of safety and efficacy. For example, JTT is clinically used in Japan to stimulate the immunological functions of cancer patients undergoing chemotherapy and radiation. Although the clinical effects of JTT are recognized, the active compounds and mechanism of action are unknown. The studies conducted previously in our laboratory associated several phytosterols and plant glycolipids with the potent immunostimulatory activity of JTT: namely, β-sitosteryl β-D-glucoside (BSSG), glucocerebroside (GluCer), digalactosyldiacylglycerol (DGDG) and monogalactosyldiacylglycerol (MGDG). However, these compounds, when further purified, exhibited little or no immunostimulatory activity. This suggested that the immunostimulatory …

Mathematical Modeling Of Nanoparticle Biodistribution, Prashant Dogra

Biomedical Sciences ETDs

The prospects of nanoparticle-based drug delivery and imaging have been hindered by insufficient understanding of the effects of nanoparticle physicochemical properties on their in vivo disposition. Here, we present an integrative mathematical modeling and in vivo imaging approach to quantify the relationship between nanoparticle physicochemical properties, namely, size, surface charge, and surface chemistry, on their in vivo disposition kinetics in healthy rats. We developed simple master equations in closed-form to accurately represent the time-dependent concentration of nanoparticles in different regions of the body and obtain functional relationships for predictive purpose to support rational design of nanomedicine. We further used …

Hyperthermia As A Cancer Treatment- From Theory To Practice, Graham Fullerton

CMC Senior Theses

Using iron super-paramagnetic and ferromagnetic nanoparticles composed of Fe₃O₄ molecules, scientists analyze the effectiveness and practicality of this new treatment theory, hyperthermia. The problems of magnetic particle density, isothermal barriers/cellular cooling thresholds, and nanoparticle specific targeting are addressed in this review.

Iron magnetic nanoparticles were chosen due to their relatively low biological reactivates and lack of subsequent cellular toxicity. However, there are significant heating problems associated with these magnetic nanoparticles due to their relative size and short thermal time constants or thermal half-lives. Effectively, these aforementioned issues create a phenomenon where cancerous cells, surrounded by unheated healthy …

Size-Dependent Inhibitory Effects Of Antibiotic Drug Nanocarriers Against Pseudomonas Aeruginosa, Feng Ding, Preeyaporn Songkiatisak, Pavan Kumar Cherukuri, Tao Huang, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Multidrug membrane transporters (efflux pumps) are responsible for multidrug resistance (MDR) and the low efficacy of therapeutic drugs. Noble metal nanoparticles (NPs) possess a high surface-area-to-volume ratio and size-dependent plasmonic optical properties, enabling them to serve both as imaging probes to study sized-dependent MDR and as potential drug carriers to circumvent MDR and enhance therapeutic efficacy. To this end, in this study, we synthesized three different sizes of silver nanoparticles (Ag NPs), 2.4 ± 0.7, 13.0 ± 3.1, and 92.6 ± 4.4 nm, functionalized their surface with a monolayer of 11-amino-1-undecanethiol (AUT), and covalently conjugated them with antibiotics (ofloxacin, Oflx) …

Multimodal Noncontact Diffuse Optical Reflectance Imaging Of Blood Flow And Fluorescence Contrasts, Daniel Irwin

Theses and Dissertations--Biomedical Engineering

In this study we design a succession of three increasingly adept diffuse optical devices towards the simultaneous 3D imaging of blood flow and fluorescence contrasts in relatively deep tissues. These metrics together can provide future insights into the relationship between blood flow distributions and fluorescent or fluorescently tagged agents. A noncontact diffuse correlation tomography (ncDCT) device was firstly developed to recover flow by mechanically scanning a lens-based apparatus across the sample. The novel flow reconstruction technique and measuring boundary curvature were advanced in tandem. The establishment of CCD camera detection with a high sampling density and flow recovery by speckle …

Raman Spectroscopic Analysis Of High Molecular Weight Proteins In Solution: Considerations For Sample Analysis And Data Pre-Processing, Drishya Parachalil, Brenda B. Brankin, Jennifer Mcintyre, Hugh Byrne

Articles

This study explores the potential of Raman spectroscopy, coupled with multivariate regression techniques and a protein separation technique (ion exchange chromatography), to quantitatively monitor diagnostically relevant changes in high molecular weight proteins in liquid plasma. Measurement protocols to detect the imbalances in plasma proteins as an indicator of various diseases using Raman spectroscopy are optimised, such that strategic clinical applications for early stage disease diagnostics can be evaluated. In a simulated plasma protein mixture, concentrations of two proteins of identified diagnostic potential (albumin and fibrinogen) were systematically varied within physiologically relevant ranges. Scattering from the poorly soluble fibrinogen fraction is …

The Microvascular And Systemic Effects Of Titanium Dioxide Nanoparticle Exposure: A Physiological Perspective, Alaeddin Bashir Abukabda

Graduate Theses, Dissertations, and Problem Reports (ETD)

Titanium dioxide nanoparticles (nano-TiO₂) are one of the most widely used engineered nanomaterials (ENM). Their ubiquitous inclusion warrants a more thorough understanding of their toxicity, particularly in sensitive populations such as pregnant women and the developing fetus.

The aim of the first study was to determine the most sensitive segments of the vasculature to pulmonary ENM exposure. Macrovascular function was investigated in the thoracic aorta, common femoral artery and 3^rd order mesenteric arterioles using wire myography. Microvascular function was assessed in 4^th and 5^th order mesenteric arterioles via pressure myography. Nano-TiO₂ exposure induced impairments …

Nanomedicine For Immunosuppressive Therapy: Achievements In Pre-Clinical Research, Hanan Al-Lawati, Hamidreza Montazeri Aliabadi, Behzad Sharif Makhmalzadeh, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Introduction: Immunosuppression is the mainstay therapy in organ transplantation and autoimmune diseases. The effective clinical application of immunosuppressive agents has suffered from the emergence of systemic immunosuppression and/or individual drug side effects. Nanotechnology approaches may be used to modify the mentioned shortcomings by enhancing the delivery of immunosuppressants to target cells of the immune system, thus reducing the required dose for function, and/or reducing drug distribution to non-target tissues.

Areas covered: We provide an overview on the development of nanotechnology products for the most commonly used immunosuppressive agents. At first, the rationale for the use of nanoparticles as …