Nanoparticle-Stabilized Capsules for the Treatment of Bacterial Biofilms

Abstract

Bacterial biofilms are widely associated with persistent infections. High resistance to conventional antibiotics and prevalent virulence makes eliminating these bacterial communities challenging therapeutic targets. We describe here the fabrication of a nanoparticle-stabilized capsule with a multicomponent core for the treatment of biofilms. The peppermint oil and cinnamaldehyde combination that comprises the core of the capsules act as potent antimicrobial agents. An in situ reaction at the oil/water interface between the nanoparticles and cinnamaldehyde structurally augments the capsules to efficiently deliver the essential oil payloads, effectively eradicating biofilms of clinically isolated pathogenic bacteria strains. In contrast to their antimicrobial action, the capsules selectively promoted fibroblast proliferation in a mixed bacteria/mammalian cell system making them promising for wound healing applications.

Keywords: Pickering emulsion; biofilm; phytochemicals; self-assembly; silica nanoparticles.

Figure 1

Confocal micrographs of a) P-Cap and b) CP-Cap. The nanoparticles’ cores are labeled with fluorescein (green fluorescence) and the oil phases are loaded with Nile red (red fluorescence). Scale bars are 20 µm. c) XPS spectra showing N 1s core levels arising from SiO₂ NPs and CP-Cap. d) Water contact angles of silica nanoparticles following incubation with varying concentrations of cinnamaldehyde.

Figure 2

Representative 3D projection of confocal image stacks of 1 day-old E. coli DH5α biofilm after 3 hrs treatment with a) CP-Cap containing FITC-labeled SiO2 NP, b) P-Cap containing FITC-labeled SiO₂ NP, and c) FITC-labeled SiO₂ NP at 20 % (v/v % of 2 % emulsion) concentration. Upper panels are projection at 247° angle turning along Y axis and lower panels are at 270° angle turning along Y axis. Scale bars are 20 µm.

Figure 3

Viability of 1 day-old a) P. aeruginosa (CD-1006) b) E. coli DH5α c) S. aureus (CD-489) d) E. cloacae complex (CD-1412) biofilms after 3 hrs treatment with CP-Cap, P-Cap, SiO2 NP, and peppermint oil at different emulsion concentrations (v/v % of 2 % emulsion). The data are average of triplicates and the error bars indicate the standard deviations.

Figure 4

Viability of 3T3 fibroblast cells and E. coli biofilms in the co-culture model after 3 hrs treatment with a) CP-Cap, b) P-Cap, c) SiO₂ NP, and d) peppermint oil at different emulsion concentrations (v/v % of 2 % emulsion). Scatters and lines represent 3T3 fibroblast cell viability. Bars represent log₁₀ of colony forming units in biofilms. The data are average of triplicates and the error bars indicate the standard deviations.

Scheme 1

a) Schematic depiction of the strategy used to generate antimicrobial capsules. Peppermint oil with dissolved cinnamaldehyde is emulsified into an aqueous suspension of amine functionalized silica nanoparticles. Cinnamaldehyde within the oil reacts with the amines on the nanoparticles at the oil/water interface to create a multimodal delivery vehicle. b) Capsules interact with biofilm through electrostatic complementarity. Capsules release their payload disrupting the biofilm, eliminating the bacteria.