(85c) Block Copolymer Nanoparticle for Biofilm Dispersal of Gram-Positive MRSA and VRE

Biofilm-associated infections have become a major threat to human health and bacteria cells inside biofilms are typically around 1000-fold more resistant to antibiotics. Therefore, the conventional antibiotics or antimicrobial peptides(AMPs) become less effective to work on the biofilm bacteria. It is our priority to develop new antibiofilm agents with good biocompatibility. In order to address this problem, a novel anti-biofilm cationic polymeric nanoparticles have been studied in our group, and these nanoparticles showed excellent antibiofilm activity and are hemolytic with good therapeutic index as well as good in vivo cytotoxicity. Dextran and poly(3-Acrylamidopropyl) trimethylammonium chloride (AMPTMA)) are both hydrophilic polymers and we attempted to explore the anti-biofilm effects of copolymers made from these, and with a minor component based on poly (butyl methacrylate) (PBMA). Four types of AMPTMA-based copolymers were made by the facile Atom Transfer Radical Polymerization (ATRP) reaction: (i) A100 which is poly(AMPTMA)100; (ii) DA100 which is a dextran-block-poly (AMPTMA)100; (iii) DAB which is dextran-block-poly (AMPTMA-co-BMA) and (iv)AB which is poly(AMPTMA-co-BMA). For DAB, it can self-assemble into nanoparticles which are 20-30 nm in diameter with the dextran block as the corona, and the poly poly(AMPTMA-co-BMA)) as core. However, the rest three polymers didn’t form this nanoparticle. Our results showed that DA95B5 copolymers with micellar nanostructure are effective in the dispersal of preformed biofilms of clinically relevant Gram-positive MRSA and Vancomycin-Resistant Enterococci (VRE V583) with low in vivo cytotoxicity. To the best of our knowledge, this is the first report of cationic polymeric micellar nanoparticle as good antibiofilm agents with effective removal of pre-formed biofilm with good biocompatibility in contrast to many other such agents which are enzyme-based.