C. B. Clemons

In vitro antimicrobial studies of silver carbene complexes: activity of free and nanoparticle carbene formulations against clinical isolates of pathogenic bacteria

OBJECTIVES Silver carbenes may represent novel, broad-spectrum antimicrobial agents that have low toxicity while providing varying chemistry for targeted applications. Here, the bactericidal activity of four silver carbene complexes (SCCs) with different formulations, including nanoparticles (NPs) and micelles, was tested against a panel of clinical strains of bacteria and fungi that are the causative agents of many skin and soft tissue, respiratory, wound, blood, and nosocomial infections. METHODS MIC, MBC and multidose experiments were conducted against a broad range of bacteria and fungi. Time-release and cytotoxicity studies of the compounds were also carried out. Free SCCs and SCC NPs were tested against a panel of medically important pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Acinetobacter baumannii (MRAB), Pseudomonas aeruginosa, Burkholderia cepacia and Klebsiella pneumoniae. RESULTS All four SCCs demonstrated strong efficacy in concentration ranges of 0.5-90 mg/L. Clinical bacterial isolates with high inherent resistance to purified compounds were more effectively treated either with an NP formulation of these compounds or by repeated dosing. Overall, the compounds were active against highly resistant bacterial strains, such as MRSA and MRAB, and were active against the biodefence pathogens Bacillus anthracis and Yersinia pestis. All of the medically important bacterial strains tested play a role in many different infectious diseases. CONCLUSIONS The four SCCs described here, including their development as NP therapies, show great promise for treating a wide variety of bacterial and fungal pathogens that are not easily killed by routine antimicrobial agents.

Nanoparticle Deposition onto Biofilms

We develop a mathematical model of nanoparticles depositing onto and penetrating into a biofilm grown in a parallel-plate flow cell. We carry out deposition experiments in a flow cell to support the modeling. The modeling and the experiments are motivated by the potential use of polymer nanoparticles as part of a treatment strategy for killing biofilms infecting the deep passages in the lungs. In the experiments and model, a fluid carrying polymer nanoparticles is injected into a parallel-plate flow cell in which a biofilm has grown over the bottom plate. The model consists of a system of transport equations describing the deposition and diffusion of nanoparticles. Standard asymptotic techniques that exploit the aspect ratio of the flow cell are applied to reduce the model to two coupled partial differential equations. We perform numerical simulations using the reduced model. We compare the experimental observations with the simulation results to estimate the nanoparticle sticking coefficient and the diffusion coefficient of the nanoparticles in the biofilm. The distributions of nanoparticles through the thickness of the biofilm are consistent with diffusive transport, and uniform distributions through the thickness are achieved in about four hours. Nanoparticle deposition does not appear to be strongly influenced by the flow rate in the cell for the low flow rates considered.

Development of the Pseudomonas aeruginosa mushroom morphology and cavity formation by iron-starvation: a mathematical modeling study.

We present a mathematical model of mushroom-like architecture and cavity formation in Pseudomonas aeruginosa biofilms. We demonstrate that a proposed disparity in internal friction between the stalk and cap extracellular polymeric substances (EPS) leads to spatial variation in volumetric expansion sufficient to produce the mushroom morphology. The capability of diffusible signals to induce the formation of a fluid-filled cavity within the cap is then investigated. We assume that conversion of bacteria to the planktonic state within the cap occurs in response to the accumulation or depletion of some signal molecule. We (a) show that neither simple nutrient starvation nor signal production by one or more subpopulations of bacteria is sufficient to trigger localized cavity formation. We then (b) demonstrate various hypothetical scenarios that could result in localized cavity formation. Finally, we (c) model iron availability as a detachment signal and show simulation results demonstrating cavity formation by iron starvation. We conclude that iron availability is a plausible mechanism by which fluid-filled cavities form in the cap region of mushroom-like structures.

Multiscale modeling, simulations, and experiments of coating growth on nanofibers. Part II. Deposition

This work is Part II of an integrated experimental/modeling investigation of a procedure to coat nanofibers and core-clad nanostructures with thin-film materials using plasma-enhanced physical vapor deposition. In the experimental effort, electrospun polymer nanofibers are coated with aluminum materials under different operating conditions to observe changes in the coating morphology. This procedure begins with the sputtering of the coating material from a target. Part I [J. Appl. Phys. 98, 044303 (2005)] focused on the sputtering aspect and transport of the sputtered material through the reactor. That reactor level model determines the concentration field of the coating material. This field serves as input into the present species transport and deposition model for the region surrounding an individual nanofiber. The interrelationships among processing factors for the transport and deposition are investigated here from a detailed modeling approach that includes the salient physical and chemical phenomena....

Mathematical modelling of Pseudomonas aeruginosa biofilm growth and treatment in the cystic fibrosis lung.

Lung failure due to chronic bacterial infection is the leading cause of death for patients with cystic fibrosis (CF). It is thought that the chronic nature of these infections is, in part, due to the increased tolerance and recalcitrant behaviour of bacteria growing as biofilms. Inhalation of silver carbene complex (SCC) antimicrobial, either encased in polymeric biodegradable particles or in aqueous form, has been proposed as a treatment. Through a coordinated experimental and mathematical modelling effort, we examine this proposed treatment of lung biofilms. Pseudomonas aeruginosa biofilms grown in a flow-cell apparatus irrigated with an artificial CF sputum medium are analysed as an in vitro model of CF lung infection. A 2D mathematical model of biofilm growth within the flow-cell is developed. Numerical simulations demonstrate that SCC inactivation by the environment is critical in aqueous SCC, but not SCC-polymer, based treatments. Polymer particle degradation rate is shown to be an important parameter that can be chosen optimally, based on environmental conditions and bacterial susceptibility.

Modeling the response of a biofilm to silver-based antimicrobial

Biofilms are found within the lungs of patients with chronic pulmonary infections, in particular patients with cystic fibrosis, and are the major cause of morbidity and mortality for these patients. The work presented here is part of a large interdisciplinary effort to develop an effective drug delivery system and treatment strategy to kill biofilms growing in the lung. The treatment strategy exploits silver-based antimicrobials, in particular, silver carbene complexes (SCC). This manuscript presents a mathematical model describing the growth of a biofilm and predicts the response of a biofilm to several basic treatment strategies. The continuum model is composed of a set of reaction-diffusion equations for the transport of soluble components (nutrient and antimicrobial), coupled to a set of reaction-advection equations for the particulate components (living, inert, and persister bacteria, extracellular polymeric substance, and void). We explore the efficacy of delivering SCC both in an aqueous solution and in biodegradable polymer nanoparticles. Minimum bactericidal concentration (MBC) levels of antimicrobial in both free and nanoparticle-encapsulated forms are estimated. Antimicrobial treatment demonstrates a biphasic killing phenomenon, where the active bacterial population is killed quickly followed by a slower killing rate, which indicates the presence of a persister population. Finally, our results suggest that a biofilm with a ready supply of nutrient throughout its depth has fewer persister bacteria and hence may be easier to treat than one with less nutrient.

Modeling and simulation of axisymmetric coating growth on nanofibers

This work is a modeling and simulation extension of an integrated experimental/modeling investigation of a procedure to coat nanofibers and core-clad nanostructures with thin film materials using plasma enhanced physical vapor deposition. In the experimental effort, electrospun polymer nanofibers are coated with metallic materials under different operating conditions to observe changes in the coating morphology. The modeling effort focuses on linking simple models at the reactor level, nanofiber level, and atomic level to form a comprehensive model. The comprehensive model leads to the definition of an evolution equation for the coating free surface. This equation was previously derived and solved under a single-valued assumption in a polar geometry to determine the coating morphology as a function of operating conditions. The present work considers the axisymmetric geometry and solves the evolution equation without the single-valued assumption and under less restrictive assumptions on the concentration field than the previous work.

Localized Corrosion Risk Assessment Using Markov Analysis

The objective of this work was to develop the foundation for an interactive corrosion risk management tool for assessing the probability of failure of equipment/infrastructure as a function of threats (such as pitting corrosion and coating degradation) and mitigation schemes (such as inhibitors and coatings). The application of this work was to assist with corrosion management and maintenance planning of equipment/infrastructure given dynamic changes in environmental conditions. Markov models are developed to estimate pitting damage accumulation density distributions as a function of input parameters for pit nucleation and growth rates. The input parameters are selected based upon characterization with experimental or field observations over a sufficiently long period of time. Model predictions are benchmarked against laboratory pitting corrosion tests and long-term atmospheric exposure data for aluminum alloys, obtained from the literature. The models are also used to examine hypothetical scenarios for t...

Experimental characterization and modeling of a nanofiber-based selective emitter for thermophotovoltaic energy conversion: The effect of optical properties

Aluminum oxide nanofibers doped with erbium oxide have been synthesized by calcining polymer fibers made by the electrospinning technique using a mixture of aluminum acetate, erbium acetate and polyvinylpyrrolidone dissolved in ethanol. The resulting ceramic fibers are used to fabricate a free-standing selective emitter. The general equation of radiation transfer coupled with experimentally measured optical properties is used to model the net radiation obtained from these structures. It has been found that the index of refraction and the extinction coefficient are direct functions of the erbia doping level in the fibers. The fibers radiated in a selective manner at ∼1.53 μm with an efficiency of about 90%. For a fiber film on a substrate, the effect of film thickness, extinction coefficient and substrate emissivity on the overall emitter emissivity is also investigated in this study. Results show that the emissivity of the film increases as the thickness of the film increases up to a maximum value, after ...

Field emission from coated nanowires

This work investigates radial field emission from an Al-coated nanowire due to a time harmonic incident electromagnetic field. An analytical expression for the electric field inside and outside a smooth nanowire is derived. Through the boundary perturbation technique, this expression is corrected to include the effects of roughness of the nanowire surface. The corrected electric field is used to calculate the potential energy of the electromagnetic field in order to estimate the resulting current density. The Wentzel-Krammers-Brillouin approximation is employed in order to estimate the tunneling probability of the electrons in the metal due to the external electromagnetic potential. For the field-emission calculations, the free-electron model is invoked. The results indicate that at sufficiently low frequencies, the perturbative corrections do not influence the critical conditions for emission or the current density.