Understanding the biocide action of poly(hexamethylene biguanide) using Langmuir monolayers of dipalmitoyl phosphatidylglycerol

Souza, Adriano Lopes de; Ceridório, Lucinéia Ferreira; Paula, Gustavo F. de; Mattoso, Luiz H. C.; Oliveira, Osvaldo N.

doi:10.1016/j.colsurfb.2015.05.018

Cited by 18 publications

(7 citation statements)

References 41 publications

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“…Hitherto, the exact antimicrobial mechanism of PHMB is still under debate. ,,− In the early studies, PHMB was believed to work through the perturbation of microbial lipid bilayers . Detailed studies prove that PHMB interacts with the anionic microbial membrane through electrostatic and hydrophobic interactions, H-bonding, or dehydration of polar groups, which impair the integrity of bacterial cell membrane and cause the death of microbes. − However, more recent studies indicate PHMB is able to enter the microbial cells and bind with the nucleic acids, which induces the arrest of cell division and condensation of chromosomes. , Therefore, PHMB may work with multimodal antimicrobial mechanisms of membrane perturbation and chromosome condensation. According to the MIC results, the increase of PEG blocks in APEG-PHMB caused a deterioration of antimicrobial activity, whereas the conjugation of allyl glycidyl ether to PHMB did not affect it (Table ).…”

Section: Resultsmentioning

confidence: 99%

Dual-Functional Polyethylene Glycol-b-polyhexanide Surface Coating with in Vitro and in Vivo Antimicrobial and Antifouling Activities

Zhi

et al. 2017

ACS Appl. Mater. Interfaces

147

108

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In recent years, microbial colonization on the surface of biomedical implants/devices has become a severe threat to human health. Herein, surface-immobilized guanidine derivative block copolymers create an antimicrobial and antifouling dual-functional coating. We report the preparation of an antimicrobial and antifouling block copolymer by the conjugation of polyhexanide (PHMB) with either allyl glycidyl ether or allyloxy polyethylene glycol (APEG; MW 1200 and 2400). The allyl glycidyl ether modified PHMB (A-PHMB) and allyloxy polyethylene glycol modified PHMB (APEG-PHMB) copolymers were grafted onto a silicone rubber surface as a bottlebrush-like coating, respectively, using a plasma-UV-assisted surface-initiated polymerization. Both A-PHMB and APEG-PHMB coatings exhibited excellent broad-spectrum antimicrobial properties against Gram-negative/positive bacteria and fungi. The APEG-PHMB coating displayed an improved antibiofilm as well as antifouling properties and a long reusable cycle, compared with two other coatings, due to its abundant PEG blocks among those copolymers. Also, the APEG-PHMB-coated silicone coupons were biocompatible toward mammalian cells, as revealed by in vitro hemocompatibile and cytotoxic assays. An in vivo study showed a significant decline of Escherichia coli colonies with a 5-log reduction, indicating the APEG-PHMB coating surface worked effectively in the rodent subcutaneous infection model. This PHMB-based block copolymer coating is believed to be an effective strategy to prevent biomaterial-associated infections.

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Section: Resultsmentioning

confidence: 99%

Dual-Functional Polyethylene Glycol-b-polyhexanide Surface Coating with in Vitro and in Vivo Antimicrobial and Antifouling Activities

Zhi

et al. 2017

ACS Appl. Mater. Interfaces

147

108

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“…Because of these attributes PHMB displays increased membrane permeability, facilitating its interaction with bacterial membranes compared to PAPB and its transfer into the cell, where it disturbs the metabolism of the micro-organisms [reviewed by Hubner & Kramer (2010) and Kaehn (2010)]. Recent research further supports the interaction with bacterial membranes as the mode of action for PHMB, stating that it disturbs the first layer of the membrane lipid bilayer (Chadeau et al, 2012) by electrostatic as well as hydrophobic interactions and dehydration (Souza et al, 2015). However, a new study also strengthened the hypothesis of additional mechanisms of the bactericidal effect of PHMB based on the interaction of the infiltrated substance with bacterial chromosomes (Chindera et al, 2016).…”

Section: Discussionmentioning

confidence: 97%

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

Rembe

Fromm‐Dornieden

Schäfer

et al. 2016

Journal of Medical Microbiology

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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.

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“…Whether SICS involves cell damage is still under debate. MPS characteristically contain a surfactant cleaner such as Tetronic 1107 [ 54 ], a biocide such as polyhexamethylene biguanide (which may also have surfactant properties [ 55 ]), and a buffering agent. Surfactants dissolve plasma membrane lipids while this may not cause significant toxicity we suggest that barrier function of the plasma membrane may be disrupted sufficiently to allow fluorescein to enter cells more freely.…”

Section: Discussionmentioning

confidence: 99%

Dynasore protects the ocular surface against damaging oxidative stress

et al. 2018

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“Vital” dyes such as fluorescein and rose bengal are used clinically to evaluate ocular surface health; however, staining mechanisms remain poorly understood. Recent evidence suggests that sublethal cell damage stimulates fluorescein dye uptake. Since damage can also stimulate reparative plasma membrane remodeling, we hypothesized that dye uptake occurs via endocytic vesicles. Using an oxidative stress model, we show that damage to relatively undifferentiated monolayer cultures of human corneal epithelial cells stimulates uptake of fluorescein and rose bengal dyes and also stimulates endocytosis. Importantly, dye uptake was blocked by co-treatment with three different endocytosis inhibitors. Damage to stratified and differentiated corneal epithelial cell cultures, which are a better model of the ocular surface, also stimulated dye uptake; however, endocytosis was not stimulated in this case, and two of the inhibitors did not block dye uptake. The exception was the inhibitor Dynasore and its more potent analogue Dyngo-4a, small molecules that target dynamin family GTPases, but also have off-target effects on the plasma membrane. Significantly, while Dynasore blocked stress-stimulated dye uptake at the ocular surface of ex vivo mouse eyes when treatment was performed at the same time as eyes were stressed, it had no effect when used after stress was applied and the ocular surface was already damaged. Thus, Dynasore could not be working by inhibiting endocytosis. Employing cytotoxicity and western blotting assays, we demonstrate an alternative mechanism, showing that Dynasore is remarkably protective of cells and their surface glycocalyx, preventing damage due to oxidative stress, and thus precluding dye entry. These unexpected and novel findings provide greater insight into mechanisms of vital dye uptake and emphasize the importance of using a differentiated cell culture model for such studies. They also suggest that Dynasore and analogues might be used therapeutically to protect the ocular surface and to treat ocular surface disease.

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Understanding the biocide action of poly(hexamethylene biguanide) using Langmuir monolayers of dipalmitoyl phosphatidylglycerol

Cited by 18 publications

References 41 publications

Dual-Functional Polyethylene Glycol-b-polyhexanide Surface Coating with in Vitro and in Vivo Antimicrobial and Antifouling Activities

Dual-Functional Polyethylene Glycol-b-polyhexanide Surface Coating with in Vitro and in Vivo Antimicrobial and Antifouling Activities

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

Dynasore protects the ocular surface against damaging oxidative stress

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