Self-assembly of amino acid-based random copolymers for antibacterial application and infection treatment as nanocarriers

Bacterial infection is one of the most significant complications worldwide and has been one of the main factors of morbidity and mortality for the chronic wounds. Considering the negative charged feature of bacterial pathogens, a positive charged poly(ester amide) (PEA) micellar system based on lysine, arginine and phenylalanine is developed. In this study, a serials of PEA random copolymers can be obtained by altering the sorts of amino acids and feed ratio, and the self-assembled PEA micelles with an average diameter ranging from 150 to 200 nm exhibit the integrated properties of excellent biocompatibility and enzymatic biodegradation. More interesting, the degraded random block micelles can reassemble into smaller sized micelles with the diameter less than 20 nm which have promising applications in drug delivery. The PEA micellar nanocarriers display an intrinsic antibacterial property due to the pendant groups of lysine and arginine based moieties and this killing capacity can be enhanced by grafting levo-floxacin without losing the original performance. The in vitro antibacterial evaluation proves all of the micelles display a concentration dependent efficiency of killing bacteria (up to 99.99%). The in vivo Staphylococcus aureus induced infection model demonstrates that the micelles are effective in killing the bacteria and infection treatment. The successful synthesis of the biocompatible and biodegradable amino acid based micellar nanocarriers may provide new insights into the development of biomedical materials for antibacterial applications and drug delivery. (C) 2018 Elsevier Inc. All rights reserved.