Amino Acid Block Copolymers with Broad Antimicrobial Activity and Barrier Properties

Antimicrobial properties of a long-chain, synthetic, cationic, and hydrophobic amino acid block copolymer are reported. In 5 and 60 min time-kill assays, solutions of K₁₀₀ L₄₀ block copolymers (poly(l-lysine·hydrochloride)₁₀₀ -b-poly(l-leucine)₄₀ ) at concentrations of 10-100 µg mL^-1 show multi-log reductions in colony forming units of Gram-positive and Gram-negative bacteria, as well as yeast, including multidrug-resistant strains. Driven by association of hydrophobic segments, K₁₀₀ L₄₀ copolymers form viscous solutions and self-supporting hydrogels in water at concentrations of 1 and 2 wt%, respectively. These K₁₀₀ L₄₀ preparations provide an effective barrier to microbial contamination of wounds, as measured by multi-log decreases of tissue-associated bacteria with deliberate inoculation of porcine skin explants, porcine open wounds, and rodent closed wounds with foreign body. Based on these findings, amino acid copolymers with the features of K₁₀₀ L₄₀ can combine potent, direct antimicrobial activity and barrier properties in one biopolymer for a new approach to prevention of wound infections.