ABSTRACT
Nine guanidinylated amphiphilic polycarbonates are rationally designed and synthesized. Each polymer has the same biodegradable backbone but different side groups. The influence of the hydrophobic/hydrophilic effect on antimicrobial activities and cytotoxicity is systematically investigated. The results verify that tuning the length of the spacer arm between the cationic guanidine group and the polycarbonate backbone is an efficient design strategy to alter the hydrophobic/hydrophilic balance without changing the cationic charge density. A spacer arm of six methylene units (CH2 )6 shows the best antimicrobial activity (minimum inhibitory concentration, MIC = 40 µg mL-1 against Escherichia coli, MIC = 20 µg mL-1 against Staphylococcus aureus, MIC = 40 µg mL-1 against Candida albicans) with low hemolytic activity (HC50 > 2560 µg mL-1 ). Furthermore, the guanidinylated polycarbonates exhibit the ability to self-assemble and present micelle-like nanostructure due to their intrinsic amphiphilic macromolecular structure. Transmission electron microscopy and dynamic light scattering measurements confirm polymer micelle formation in aqueous solution with sizes ranging from 82 to 288 nm.
Subject(s)
Anti-Bacterial Agents/pharmacology , Guanidine/pharmacology , Micelles , Polycarboxylate Cement/pharmacology , Surface-Active Agents/pharmacology , Animals , Guanidine/chemical synthesis , Guanidine/chemistry , Hemolysis/drug effects , Microbial Sensitivity Tests , Piperazines/chemistry , Polycarboxylate Cement/chemical synthesis , Polycarboxylate Cement/chemistry , Sheep , Surface-Active Agents/chemical synthesis , Surface-Active Agents/chemistryABSTRACT
Six guanidine functionalized aliphatic biodegradable polycarbonates with varying molecular weights and charge densities were synthesized via postsynthesis modification of alkyne containing polycarbonates using Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry. The concept of passive diluting group was to modify the cationic charge density of the polycarbonate without changing its hydrophilicity. Within the molecular weight range from 8000 to 30000 g mol-1, these guanidine polycarbonates exhibited broad-spectrum biocidal activity with low toxicity to red blood cells (RBCs). The lowest molecular weight homopolymer sample (PG-8k-100) showed the best antimicrobial activity (MIC = 40 µg/mL against Escherichia coli and MIC = 20 µg/mL against Staphylococcus epidermidis) and least RBC toxicity (0.6% hemolysis at MIC). Within the three guanidine charge densities from 20% to 70%, the low to medium dilution samples (PG-8k-7030 and PG-8k-5050) had no obvious loss in antimicrobial activities compared to the nondiluted control sample PG-8k-100. However, upon further dilution, PG-8k-2080 gave the lowest antimicrobial activity.