Direct assembly of antimicrobials within layer-by-layer films mediated by polyphosphazene polyelectrolytes*

We explore the effects of chain flexibility, charge density, and hydrophobicity on the direct, electrostatic assembly of small molecules with biocompatible polyelectrolytes. Films were assembled by the layer-by-layer (LbL) technique using ionic polyphosphazenes (PPzs) as polyanions and small-molecule antibacterial bioactives as cations. Evolution of dry film thickness was monitored with spectroscopic ellipsometry. PPz/bioactive films grew linearly in a pH dependent manner, which was correlated with ionization degree of PPzs in the films using ATR-FTIR. Deposition and release of bioactives were strongly dependent on charge density and hydrophobicity of polyanions; these effects were compared for the cases of non-fluorinated and fluorinated PPzs. The release rate of bioactives from films was explored as a function of temperature (ambient, physiological, and accelerated (65 °C)) and pH. Non-fluorinated PPz films released antibiotics at low pH following the charge renormalization argument. In contrast, multilayers of fluorinated PPzs enabled antimicrobial retention, due to the enhanced hydrophobic interactions.