Self-Defensive Layer-by-Layer Films with Bacteria-Triggered Antibiotic Release

Abstract

We report on highly efficient, bioresponsive, controlled-release antibacterial coatings constructed by direct assembly of tannic acid (TA) with one of several cationic antibiotics (tobromycin, gentamicin, and polymyxin B) using the layer-by-layer (LbL) technique. These films exhibit a distinct “self-defense” behavior triggered by acidification of the immediate environment by pathogenic bacteria, such as Staphylococcus epidermidis (S. epidermidis) or Escherichia coli (E. coli). Films assembled using spin-assisted and dip-assisted techniques show drastically different morphology, thickness and pH-/bacteria-triggered antibiotic release characteristics. While dip-deposited films have rough surfaces with island-like, granular structures regardless of the film thickness, spin-assisted LbL assemblies demonstrate a transition from linear deposition of uniform 2D films to a highly developed 3D morphology for films thicker than ∼45 nm. Ellipsometry, UV–vis and mass spectrometry confirm that all coatings do not release antibiotics in phosphate buffered saline at pH 7.4 for as long as one month in the absence of bacteria and therefore do not contribute to the development of antibiotic resistance. These films do, however, release antibiotics upon pH lowering. The rate of triggered release can be controlled through the choice of assembled antibiotic and the assembly technique (spin- vs dip-deposition) and by the spinning rate used during deposition, which all affect the strength of TA–antibiotic binding. TA/antibiotic coatings as thin as 40 nm strongly inhibit S. epidermidis and E. coli bacterial growth both at surfaces and in surrounding medium, but support adhesion and proliferation of murine osteoblast cells. These coatings thus present a promising way to incorporate antibacterial agents at surfaces to prevent bacterial colonization of implanted biomedical devices.

Harnessing the Multifunctionality in Nature: A Bioactive Agent Release System with Self‐Antimicrobial and Immunomodulatory Properties

“…[ 13 ] Polyelectrolyte multilayers are versatile nano to microscale coatings that have been used widely as delivery systems. [14][15][16][17] Consecutive dipping of implant surfaces to polycation and polyanion solutions with intermittent rinsing steps leads to formation of thin fi lms due to the interactions of polyanions and polycations. These fi lms can be further loaded with bioactive agents for their controlled release.…”

Biofunctionalization of surfaces using polyelectrolyte multilayers

“…For example, films were constructed by direct assembly of tannic acid (partially ionized at pH 7.5), combined with cationic antibiotics. These coatings stayed stable in phosphate-buffered saline at pH 7.4 for as long as 1 month in the absence of bacteria and released antibiotics only upon pH lowering [64]. More recently, PAAgentamicin/PEI multilayer films were constructed via the LbL self-assembly method.…”

Biofunctionalization of surfaces using polyelectrolyte multilayers

“…For example, films were constructed by direct assembly of tannic acid (partially ionized at pH 7.5), combined with cationic antibiotics. These coatings stayed stable in phosphate-buffered saline at pH 7.4 for as long as 1 month in the absence of bacteria and released antibiotics only upon pH lowering [64]. More recently, PAA-gentamicin/PEI multilayer films were constructed via the LbL self-assembly method.…”