Comparing two polymeric biguanides: chemical distinction, antiseptic efficacy and cytotoxicity of polyaminopropyl biguanide and polyhexamethylene biguanide

Abstract

In this study, polyaminopropyl biguanide (PAPB) was compared to the molecularly closely related polyhexamethylene biguanide (PHMB) with respect to chemical relationship, antiseptic efficacy and cytotoxicity in vitro. Cytotoxicity for human keratinocytes (HaCaTs) and murine fibroblasts (L929) was determined according to ISO EN 10993-5 for both substances. Antimicrobial efficacy tests were performed via determination of the MBC, quantitative suspension method for substances and investigation of two PAPB-or PHMB-containing dressings against Staphyloccoccus aureus, Escherichia coli and Pseudomonas aeruginosa, according to international standards. Prior mass spectrometry was performed for chemical differentiation of the investigated substances. PHMB showed high toxicity even in low concentrations for both tested cell lines and a high antimicrobial efficacy against S. aureus and E. coli. In the case of PAPB, no or only low cytotoxicity was detected after 72 h, whilst comparable antibacterial features are lacking, as PAPB showed no relevant antimicrobial effects. Even though chemically closely related, PAPB proved to be ineffective in bacterial eradication, whilst PHMB showed a high efficacy. The discovery and establishment of safe and effective alternative antiseptics are important issues for the treatment of infected wounds. In particular, rising bacterial resistances to established agents, as well as ongoing discussions of potential toxic or carcinogenic effects emphasize this necessity. Nevertheless, the presented results highlight that even small changes in the chemical structure of related agents such as PHMB and PAPB can dramatically affect their efficacy and, therefore, need to be carefully distinguished and assessed side by side.

Biocide Exposure Induces Changes in Susceptibility, Pathogenicity, and Biofilm Formation in Uropathogenic Escherichia coli

“…While PHMB was shown to be the second most cytotoxic biocide tested, it exhibited a relatively low rf value, resulting in the highest BI value out of all the test biocides. PHMB has previously shown low-level cytotoxicity toward mammalian cells, including L929 cells, which is suggested to be due to the interaction of the biocide with the mammalian cell membrane, leading to membrane damage (44). BAC was the second least cytotoxic biocide tested and showed the second highest level of antimicrobial activity in the presence of serum in the quantitative suspension tests.…”

Survival and detection of Bacillus cereus in the presence of Escherichia coli, Salmonella enteritidis, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans after rechallenge in make‐up removers

“…Product C also contained polyaminopropyl biguanide and citric acid in addition to potassium sorbate and sodium benzoate. Polyaminopropyl biguanides, which are polymeric biguanides consist of polycationic linear polymers with a hydrophobic backbone and multiple cationic groupings separated by methylene chains , are used widely to control microbes in pharmacological formulations and cosmetics . Their antibacterial action is believed to result from rapid binding of multiple positively charged domains to the negatively charged cell membranes of both Gram‐negative and Gram‐positive bacteria, which bridges acidic phospholipids through the hydrophobic methylene groups.…”

Safety Assessment of Polyaminopropyl Biguanide (Polyhexamethylene Biguanide Hydrochloride) as Used in Cosmetics

“…with respect to antiseptic efficacy and cytotoxicity in vitro. 32 Antimicrobial efficacy tests were performed via determination of the minimum bactericidal concentration. Polyaminopropyl Biguanide (PHMB; C6) exhibited high antimicrobial activity against Staphylococcus aureus and Escherichia coli (minimal bactericidal concentration 0.05 mg/mL [0.005%]), whereas polyaminopropyl biguanide (C3) proved to be ineffective in bacterial eradication.…”

“…Cytotoxicity was evaluated in human keratinocytes (HaCaTs) and murine fibroblasts (L929). 32 In fibroblast or keratinocyte cultures, concentrations for both test substances ranged from 0.005% to 1% vol/vol. Polyaminopropyl biguanide (C3) was also tested at concentrations ranging from 0.25% to 3% vol/vol.…”