Materials with nanoscale dimensions offer several important benefits over bulk materials (e.g. increased surface area, low-cost, deviation from bulk properties, etc.). Such materials are critical components for next-generation energy storage materials, optoelectronic devices, and catalyst systems. However, these materials are often processed in liquid media, and their diminutive structures are fragile in the presence of capillary forces. As such, preparing uniform and stable nanomaterial coatings is a significant challenge. Herein, we discuss an approach where the substrate itself is factored into the assembly and growth of these materials. First, nanoporous surfaces were utilized to achieve a uniform deposition of one-dimensional (1D) and two-dimensional (2D) nanomaterials for high performance transparent conductive films. Suspensions of silver nanowires (AgNWs, 1D) and graphene oxide (GO, 2D) were deposited on superhydrophilic surfaces, which we generated through layer-by-layer assembly. It was discovered that coating defects (e.g., coffee-ring effect) were suppressed by the rapid wetting of suspensions into a thin liquid sheet on superhydrophilic surfaces. Uniform composite films were fabricated which exhibited a low sheet resistance and high percent transmittance, with minimal surface roughness. The growth of conformal Au coatings on the AgNW network stabilized the film against oxidation and granted mechanical stability through subsequent aqueous processing. Next, metal organic frameworks (MOFs) on with accessible open-metal sites were grown on electrospun hydrogel fibers (EHFs), with the fibers playing a role in their formation and stable surface bonding. Crystalline MOFs with tunable dimensions were grown on EHFs composed of crosslinked polyallylamine and polyacrylic acid. The physical properties of the fibers, such as polymer composition and the fiber diameter, had a direct role in the tuning of the MOF size and distribution on the EHFs. Last, the controlled growth of self-supported tungsten metal oxide nanosheets was investigated. Their potential as electrocatalysts and as high surface-area supports for other materials is discussed. Through salt-mediated growth, the macroscopic nanosheets of alkali (K+, Rb+, or Cs+) intercalated oxides could be produced uniformly on various tungsten metal surfaces. Anodization to adjust the surface texture altered the wettability and facilitated even salt deposition on these surfaces, resulting in a uniform nanosheet growth.

Over time, noble-metal nanostructures have sparked interest as peroxidase mimics for in-vitro diagnostics, with emphasis on inflammatory pathogenesis such as cancer. Recent advancements focusing on improving the catalytic efficiency of currently used synthetic and natural peroxidases towards future clinical applications such as Point of Care (POC) settings are being studied. Efforts in exploiting the size-dependent and physicochemical properties of noble metal nanoparticles to achieve superior catalytic performance may serve as excellent alternatives to traditional peroxidases. Here, we introduce a facile protocol to engineer citrate-capped iridium nanoparticles (Ir NPs) to study their efficacy as peroxidase mimics towards future applications as secondary antibody-labels in in-vitro diagnostic (IVD) techniques. Our inspiration for choosing to explore Ir NPs stems from the following (i) recent studies demonstrating Ir-based nanostructures with excellent catalytic performance (ii) the successful catalytic decomposition of hydrogen peroxide in the presence of Ir, revealing peroxidase-like behavior, (iii) activity of Ir NPs at high temperatures, rendering them stable and promising for hydrothermal synthesis. In this work, we successfully engineered citrate-capped Ir NPs with superior catalytic efficiency at the level of 106 – 107 s-1. We hope this work serves as an inspiration to explore the implementation of Ir NPs in practical applications.

A polymer and metal-based microfabrication technology were fabricated toward 3D Microelectrode Arrays (3D MEAs) with tri-modal functionality for obtaining simultaneous data sets comprising electrical, optical, and microfluidic markers from a variety of electrogenic cellular constructs. 3D MEAs are the next-generation interfaces to transduce multi-modal data sets from the burgeoning field of "organ-on-a-chip" in vitro modeling of biological functions. The microfabrication process is fully characterized, including key processes of microdrilling/micromilling for low and higher density 3D electrodes/ microfluidic (μF) ports along with full spectrum impedance and RMS noise showcasing the ability to control the 3D microelectrode size. Further the material set used in the microfabrication process is characterized for biological metrics through both a novel transparency assay along with a biocompatibility assay with multiple electrogenic cell culture systems. Impedance metrics showcasing morphology and spread of electrogenic cells are further analyzed. Lastly, rapid neuronal spheroid attachment to the 3D microfluidic ports of the tri-modal 3D MEA is demonstrated successfully.

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 and surface charge were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM) and zeta potential measurements. Conditions such as ionic stability and pH stability were optimized to achieve high drug loading efficiency. Cell uptake and cytotoxicity studies were used to determine the efficiency of the nanoparticles as drug delivery vehicle.

Wound treatment remains one of the most prevalent and economically burdensome healthcare concerns, often complicated by prolonged inflammation and bacterial infection, contributing to morbidity and mortality. Agents commonly used to treat chronic wound infections are limited due to their toxicity, multifactorial etiology of chronic wounds, deep skin infections, lack of sustained controlled delivery of drugs, and development of drug resistance. LL37 is an endogenous host defense peptide that has been shown to exhibit antimicrobial activity and is involved in the modulation of wound healing. Serpin A1 (A1) is a neutrophil elastase inhibitor and has been shown to demonstrate wound-healing property. Hence, our goal was to develop a topical combination nanomedicine for the controlled sustained delivery of LL37 and A1 that at precise combination ratios will significantly promote wound closure, reduce bacterial contamination, and enhance anti-inflammatory activity. We have successfully developed a solid lipid nanoparticle (SLN) formulation that can simultaneously deliver LL37 and A1 at specific ratios resulting in accelerated wound healing by promoting wound closure in BJ fibroblast cells and keratinocytes as well as synergistic enhancement of antibacterial activity against S. aureus and E. coli in comparison to LL37 or A1 alone. / May 2016

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 MEAs were further characterized in dynamic impedance measurement experiments and with an artificial skin model demonstrating their potential for wearable bioelectronics. In the second part of the thesis, microfabrication of the 3D metal MEAs for in vitro cell constructs is reported. These were fabricated using laser micromachining in 2D and transitioned out-of-plane to the final 3D conformation by a custom fabricated Hypodermic Needle Array (Hypo-Rig). The 3D metal MEAs were packaged on multiple substrates, and a 3D insulation layer was defined to fabricate microelectrodes that were subsequently characterized mechanically and electrically.

Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV). The efficacy of oral acyclovir is limited as a result of its low bioavailability (15-30%) as it is poorly water soluble and therefore requires a frequent dosing regimen. When orally administered, peak plasma concentration occurs after 1.5–2.5 hours, while its elimination half-life is approximately 2-3 hours. Acyclovir displays poor solubility in water and in lipid bilayers, which leads to poor drug levels at target sites after oral, local, or parenteral administration. In order to improve this lack of solubility, novel amphiphilic derivatives have been designed to form nanoparticles, which allow for the efficient encapsulation of this hydrophobic antiviral agent. Reformulation of drugs in liposomes has provided an opportunity to enhance the therapeutic indices of various agents mainly via alteration of their bio-distribution. Liposomal drug delivery systems have received considerable attention due to their immense advantages which include, effective encapsulation of both small and large molecules that have a wide range of hydrophobicity levels and pKa values, prolonging and targeting release of therapeutic agents by modification of liposomal surface and also minimising clinical drug dose thus reducing toxicity effects. Liposomes exhibit a number of special biological characteristics, including specific interactions with biological membranes and various cells, hence, liposomes are used as biocompatible carriers to improve delivery properties across mucus membranes. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. The aim of this study was to develop an acyclovir liposomal mucoadhesive film by actively encapsulating acyclovir into liposomes and preparing a mucoadhesive film to optimise delivery of acyclovir liposomes at target sites. To actively encapsulate acyclovir and prepare the acyclovir-containing liposomes, a comprehensive statistical methodology was used in optimising the liposome formulation to encapsulate acyclovir. Central composite design was used as the response surface methodology statistical tool to design and develop an optimised method for active encapsulation of acyclovir into liposomes. The predicted optimised encapsulation parameters were incubation temperature of 60 °C and incubation time of 45 minutes. The mean percentage encapsulation calculated was 27.72%. The overall average size of the liposomes was 99.5 nm with a narrow distribution polydispersity index of 0.105 and were physically characterised as small unilamellar vesicles which possessed an average zeta potential of -45.6 mV. High Performance Liquid Chromatography (HPLC) was used to analyse and determine acyclovir drug content in the liposomes and drug release pattern from the mucoadhesive film. Polyvinyl-pyrrolidone (PVP) and Polyethylene glycol (PEG) were used in the preparation of mucoadhesive film, in which the acyclovir encapsulated liposomes were incorporated. The average amount of acyclovir drug content quantified to be in 4 cm2 of the mucoadhesive film was 36.8543 μg. The average tensile strength of the mucoadhesive film was determined to be 3.06 N/mm2 with an elongation percentage of 4.54%. The toughness of the film was 71.50 N.mm and the force required to rupture film was 16.49 N. The work and maximum force required to detach the mucoadhesive film from the glass side was 2.58 N.mm and 11615.32 mN, respectively. A Franz diffusion cell was used to perform acyclovir drug release studies from the mucoadhesive film and a commercial brand of acyclovir cream (Acitop®). Percentage acyclovir drug release from the film and cream was plotted against time using Sigmaplot® software version 13 following First order, Peppas, Hixon and Crowell, Higuchi (Square Root Time) and Bakers and Lonsdale mathematical models. The mucoadhesive film acyclovir attained the highest correlation coefficient r2 of 0.9879 following the Baker & Lonsdale mathematical model which describes controlled drug release from spherical matrices hence fits the model as the acyclovir is encapsulated in liposomes which are incorporated in the polymer mucoadhesive film. And the acyclovir cream (Acitop®) attained the highest correlation coefficient r2 of 0.9944 following the Peppas mathematical model. The Peppas model has been used to describe drug release from various release dosage forms when there is more than one type of dosage release or when release mechanism is not well known. One assumption of this model is that drug release occurs in one dimension, which is a suitable release profile for the cream as it is absorbed through the skin in one dimension when applied topically. There was significant difference between the drug release data for the mucoadhesive film and the acyclovir cream (Acitop®). A physically stable mucoadhesive film containing acyclovir-loaded liposomes was developed.

No description available.

Historically, quantum dots (QDs) have generated tremendous excitement as a contrast agent, diagnostic tool, and even as a therapeutic in the 40 years since their discovery. Their brightness, narrow and tunable emission peaks, and large surface area for functionalization are all ideal properties for biomedical applications. However, there still are no clinically approved therapies utilizing QDs, and the toxicity of these systems have turned much of the excitement to disillusionment. In this thesis work, I outline some of the key barriers that have prevented QD translation to clinical settings — namely, proper toxicology assessment and bioaccumulation — and demonstrate some potential strategies to overcome these barriers. In the first aim, I show that copper indium sulfide (CIS, CuInS2) QDs are actually toxic, in contrast to previous literature that assumed non-toxicity. This result emphasizes how toxicity evaluation must be done carefully with proper separation of QD components (core, shell, and surface coating) that can influence or confound results. I also show that the toxicity of CIS QDs was linked to their degradation in vitro, highlighting the second barrier. In the second aim, I describe a novel, controlled synthesis of bornite (CuxFeS4) nanocrystals (NCs) with various Cu:Fe ratios and sizes and explore how those variables influence the optical properties of bornite. I also show the mechanism for the development of a localized surface plasmon resonance (LSRP) peak in bornite during oxidation, linking it to iron expulsion from the NCs and a subsequent rise in excess hole carriers. Finally, in my third aim I look at how copper iron sulfides are biodegradable, non-toxic, and useful for photothermal treatment. I demonstrate this premise through the selective lysis of bacterial cells using a NC-peptide platform that couples the targeting power of antimicrobial peptides with the photothermal capacity of bornite NCs.

The emergence of multidrug-resistant (MDR) strains of bacteria and the lack of a novel class of antibiotics has become a global health concern. Pseudomonas aeruginosa is one common MDR bacteria responsible for nosocomial infections and related mortality worldwide. It has developed resistance against commonly available antibiotics and is in the WHO's priority list of bacteria for which new antibiotics are desperately needed. Currently there is a growing interest in developing metal and non-metal-based nanoparticles to target multidrug-resistant bacteria. The objective of this study is to evaluate the efficacy of a novel nanocomposite of two non-traditional antimicrobials: a metal (Ga-III) and a non-metal (chitosan nanoparticle) against P. aeruginosa. It was hypothesized that Gallium (III) nitrate in combination with hydrothermally-treated chitosan biopolymer, which has been widely studied for wound-healing applications, will exhibit synergistic antibacterial activity due to increased modes of action . The Ga(III) nitrate is an FDA approved drug that is used to lower blood levels of calcium in some cancer patients. The drug has been under clinical trials as an antimicrobial agent due to its Iron(III) mimicking property. The chitosan-gallium nanocomposite was synthesized using hydrothermal treatment in acidic conditions. Particle size, surface charge, optical properties, and chemical interactions between Ga (III) and chitosan were studied using Dynamic Light Scattering (DLS), FT-IR, UV-VIS and Fluorescence techniques. Microplate Alamar Blue Assay, Colony Forming Unit assay and Crystal Violet biofilm inhibition assay were conducted to study the antibacterial and antibiofilm properties of the nanocomposite in aqueous suspension (pH 5.7). UV-Visible and fluorescence spectra suggested the formation of optically-active chitosan-gallium nanocomposite, exhibiting broad absorption band (~290-325 nm) and emission at 422 nm. FTIR study confirmed the depolymerization of chitosan and gallium complexation through primary amine groups of chitosan. DLS analysis showed that primary particles have hydrodynamic diameter of 141 nm and average zeta potential of +46 mV at pH 5.7. Microplate alamar blue assay revealed the MIC of the composite to be 32 µg/ml while CFU assay determined the MBC to be 128 µg/ml against P.aeruginosa. Compared to the controls chitosan and gallium nitrate, the chitosan-gallium nanocomposite showed enhanced antibacterial efficacy. Furthermore, there was 21.5% inhibition of biofilm formation at 8 µg/ml of the composite. These preliminary findings suggest the potential of chitosan-gallium nanocomposite as an effective antibacterial agent against P.aeruginosa infections.