Study of Gelation for Biodegradable Polyelectrolytes By a Counter Ion Exchange Approach

Abstract

Cationic polymers are promising as a new class of antimicrobials to combat a threat of emerging drug-resistant superbugs because multiple positive charges are effective in electrostatic interaction with negatively charged bacterial cell membranes, which leads to membrane disruption.1) Since this mechanism is fundamentally different from those of most conventional antibiotics that target inhibition of an intracellular function of bacteria, these antimicrobial polymers are believed not to contribute to development of drug resistance. Originating from the first report by Nederberg et al.,2) a series of biodegradable antimicrobial polycarbonates have been developed, and biodegradability and bioabsorbability have been recognized important for antimicrobials that injection into the body is assumed. We also have recently developed cationic antimicrobial polycarbonates tagging primary ammonium salts and a hydrophobic moiety at the side chains. These polymers exhibit antimicrobial activity and biocompatibility tuned by sequence, composition, and structure of hydrophobic comonomer units. Moreover, microbial colonization and biofilm formation on biomedical implants and devices are now acknowledged as a more severe threat and cause financial challenges for patients. Bacterial biofilm comprising complex exopolysaccharides matrix is difficult to destroy and thus serves as barriers against antibiotics. Antimicrobial hydrogels are envisioned to be an effective weapon to counter the biofilm problem.3) Biodegradable antimicrobial hydrogels are the current focus of our research because they are expected to be used for both inside and outside of the body, e.g., wound dressings for burn treatment and surface treatment of long-term implants such as catheters. In this study, we report a simple yet effective approach to generating charged biodegradable hydrogels using a counter anion exchange approach. By using di- or tri-carboxylic acids as a counter anion for a cationic ammonium group as well as a cross-linker, a cationic polymer network may be formed. Preliminary, we have already been successful to switch a counter carboxylate of the cationic polycarbonate. To form hydrogels, physical cross-linking points and balance of (de)hydration should be rationally controlled. Thus, we explore several combinations for cationic copolycarbonates with different compositions and hydrophobic side chains and di- and tri-carboxylic acids as shown in Figure 1. In addition, a chemically crosslinked cationic polycarbonate is examined for comparison. 1) Palermo, K. Kuroda, Appl. Microbial. Biotechnol. 2010, 87, 1605-1615. 2) Nederberg et al., Nature Chem. 2011, 3, 409-414. 3) Li et al., Angew. Chem. Int. Ed., 2013, 52, 674-678. Figure 1