Nanoparticle Deposition onto Biofilms

Abstract

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.

High-Velocity Microsprays Enhance Antimicrobial Activity in Streptococcus mutans Biofilms

“…Previous studies in biofilm permeability using fluorescent beads are consistent with our data showing that the beads penetration was limited to the outer biofilm layers (20-30% of the biofilm thickness) (Drury et al 1993a;Drury et al 1993b) or needed timescales up to hours to reach up 90-95% biofilm substratum by diffusion alone (Miller et al 2013), in which case some of the effect could be "overgrowth" of the biofilm as seen by Chew et al (Chew et al 2014). mins to reach half of the biofilm thickness (Corbin et al 2011;Nance et al 2013).…”

“…After exposure, the biofilms were fixed with 4% Paraformaldehyde ( Figure 1C). To quantify the penetration of the beads into the biofilm we used a relative depth ratio (RD BEADS ) to account for differences in biofilm thickness at each XY pixel location on the substratum, as explained previously (Miller et al 2013) (Supplemental material 2).…”

Lipid and polymer nanoparticles for drug delivery to bacterial biofilms

“…[124] Confocal microscopy was also the method of choice of Miller et al to investigate the deposition of pegylated L-tyrosine polyphosphate (LTP) microparticles onto P. aeruginosa biofilms in a flow cell. [125] Z-stacks were recorded after infusion of the fluorescently labeled LTP nanoparticles with an average diameter of 1.2 µm. The particles were mostly located at the fluid-biofilm interface up to 2 hours after deposition.…”

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

“…This release rate is derived from Hopfenberg (1976), assuming each particle is uniform and spherical with radius R. The constants k and C L represent the decay rate and particle loading, respectively. Our previous work (Miller et al, 2013) demonstrated that LTP particles distribute uniformly throughout the biofilm. We therefore take particle positions x i to be uniformly distributed.…”

“…Some work has already been conducted with regard to these issues. Miller et al (2013) considered biofilm-particle interaction in a flow-cell environment. Stine et al (2012) estimated what LTP particle concentrations one might have to achieve to reach a known minimal inhibitory concentration (MIC) value for the SCC drug.…”