Optimizing the Bacteriostatic and Cytocompatibility Properties of Poly(hexamethylene guanidine) Hydrochloride (PHMG) via the Guanidine/Alkane Ratio

• Published in: Biomacromolecules Vol. 23; no. 5; pp. 2170 - 2183
• Main Authors: Rao, Yu, Wang, Jinghong, Wang, Huanhuan, Wang, Hong, Gu, Rong, Shen, Jie, Hao, Qing, Brash, John L., Chen, Hong
• Format: Journal Article
• Language: English
• Published: United States 09.05.2022
• Subjects: Alkanes; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibacterial properties; biocompatibility; composite polymers; copolymerization; cross infection; emulsions; Guanidine - chemistry; Guanidine - pharmacology; guanidines; Guanidines - pharmacology; health services; Humans; hydrophobicity; Mammals; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; molecular weight; Polymers - chemistry; Polymers - pharmacology; polyurethanes; Pseudomonas aeruginosa
• ISSN: 1525-7797; 1526-4602; 1526-4602
• DOI: 10.1021/acs.biomac.2c00233

The emergence of "superbugs" is not only problematic and potentially lethal for infected subjects but also poses serious challenges for the healthcare system. Although existing antibacterial agents have been effective in some cases, the side effects and biocompatibility generally present difficulties. The development of new antibacterial agents is therefore urgently required. In this work, we have adapted a strategy for the improvement of poly(hexamethylene guanidine) hydrochloride (PHMG), a common antibacterial agent. This involves copolymerization of separate monomer units in varying ratios to find the optimum ratio of the hydrocarbon to guanidine units for antibacterial activity. A series of these copolymers, designated as PGB, was synthesized. By varying the guanidine/hydrophobic ratio and the copolymer molecular weight, a structure-optimized PGB was identified that showed broad-spectrum antibacterial activity and excellent biocompatibility in solution. In an antibacterial assay, the copolymer with the optimum composition (hydrophobic unit content 25%) inhibited >99% and was compatible with mammalian cells. A polyurethane emulsion containing this PGB component formed transparent, flexible films (PGB-PU films) on a wide range of substrate surfaces, including soft polymers and metals. The PGB-PU films showed excellent bacteriostatic efficiency against nosocomial drug-resistant bacteria, such as and methicillin-resistant (MRSA). It is concluded that our PGB polymers can be used as bacteriostatic agents generally and in particular for the design of antibacterial surfaces in medical devices.