Gallium-loaded dissolvable microfilm constructs that provide sustained release of Ga3+ for management of biofilms

摘要

The persistence of bacterial biofilms in chronic wounds delays wound healing. Although Ga³⁺ can inhibit or kill biofilms, precipitation as Ga(OH)3 has prevented its use as a topical wound treatment. We report the design of a microfilm construct comprising a polyelectrolyte film that releases non-cytotoxic concentrations of Ga³⁺ over 20 days and a dissolvable micrometer-thick film of polyvinylalcohol that enables facile transfer onto biomedically important surfaces. By using infrared spectroscopy, we show that the density of free carboxylate/carboxylic acid and amine groups within the polyelectrolyte film regulates the capacity of the construct to be loaded with Ga³⁺, and that the density of covalent cross-links introduced into the polyelectrolyte film (amide-bonds) controls the release rate of Ga³⁺. Following transfer onto the wound-contact surface of a biologic wound dressing, an optimized construct is demonstrated to release of ~0.7 µg cm⁻² day⁻¹ of Ga³⁺ over 3 weeks, thus continuously replacing Ga³⁺ lost to precipitation. The optimized construct inhibited formation of P. aeruginosa (two strains; ATCC 27853 and PA01) biofilms for up to 4 days and caused pre-existing biofilms to disperse. Overall, this study provides designs of polymeric constructs that permit facile modification of the wound-contacting surfaces of dressings and biomaterials to manage biofilms.