Amino Acid Block Copolymers with Broad Antimicrobial Activity and Barrier Properties

Abstract

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 K100L40 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, K100L40 copolymers form viscous solutions and self‐supporting hydrogels in water at concentrations of 1 and 2 wt%, respectively. These K100L40 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 K100L40 can combine potent, direct antimicrobial activity and barrier properties in one biopolymer for a new approach to prevention of wound infections.

Current Status of In Vitro Models and Assays for Susceptibility Testing for Wound Biofilm Infections

“…The method only uses drops of 10 or 20 µL that are spotted on the agar plate which allows for plating of different dilutions on one plate [145]. The results are commonly reported as the number of colony forming units per area (CFU/cm 2 ), per volume (CFU/mL), or reduction with respect untreated biofilms (log reduction) [146,147]. While colony counting remains the standard for determining the viability of microorganisms, it is a labor- and resource-intensive process [148].…”

Overview of Host Defense Peptides and Their Applications for Plastic and Reconstructive Surgeons

“…This indication is particularly appealing because HDPs and related polymers have been successfully used to prevent biofilm formation, which substantially contributes to hardware infections and the resistance of those infections to systemic antimicrobial agents. 100,101 Promising results were obtained using coatings based on melittin-cecropin peptides, which can be applied to a variety of surfaces and maintains is antimicrobial activity while minimizing host toxicity. 102 Covalently-bound coatings of amphiphilic cationic peptides have also been demonstrated to have efficacy against several bacterial pathogens and can prevent the formation of biofilms.…”

From Polymers to Functional Biomaterials

“…Moreover these polypeptide hydrogels provide an effective barrier to microbial contamination of wounds, as displayed 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. Therefore, this outstanding work perfectly demonstrates the process of development of a polymeric antimicrobial biomaterial from its synthesis to in vitro and in vivo evaluation …”