Polyhexamethylene biguanide (PHMB) is a cationic biocide. The antibacterial mode of action of PHMB (at concentrations not exceeding its minimal inhibitory concentration) upon Listeria innocua LRGIA 01 was investigated by Fourier transformed infrared spectroscopy and fluorescence anisotropy analysis. Fourier transformed infrared spectra of bacteria treated with or without PHMB presented some differences in the lipids region: the CH(2)/CH(3) (2924 cm(-1)/2960 cm(-1)) band areas ratio significantly increased in the presence of PHMB. Since this ratio generally reflects membrane phospholipids and membrane microenvironment of the cells, these results suggest that PHMB molecules interact with membrane phospholipids and, thus, affect membrane fluidity and conformation. To assess the hypothesis of PHMB interaction with L. innocua membrane phospholipids and to clarify the PHMB mode of action, we performed fluorescence anisotropy experiments. Two probes, 1,6-diphenyl-1,3,5-hexatriene (DPH) and its derivative 1-[4-(trimethyl-amino)-phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH), were used. DPH and TMA-DPH incorporate inside and at the surface of the cytoplasmic membrane, respectively. When PHMB was added, an increase of TMA-DPH fluorescence anisotropy was observed, but no changes of DPH fluorescence anisotropy occurred. These results are consistent with the hypothesis that PHMB molecules perturb L. innocua LRGIA 01 cytoplasmic membrane by interacting with the first layer of the membrane lipid bilayer.
Oil-in-water (o/w) emulsions containing egg yolk phosphatidylcholine (EPC) were combined with aqueous polyhexamethylene biguanide hydrochloride (PHMB). The PHMB concentration in the aqueous phase was estimated by filtration centrifugation experiments. In parallel, PHMB concentration was assessed utilizing cytotoxicity assays (neutral red) on cultured murine fibroblasts (L929 cells) and tests of bactericidal efficacy on either Pseudomonas aeruginosa or Staphylococcus aureus. Biological tests were performed in cell culture medium. Filtration centrifugation experiments demonstrated much higher aqueous PHMB concentrations than did the assays for biologically effective PHMB. Therefore, biological test systems should preferably be used to verify effective PHMB concentrations. Tests of microbicidal efficacy in which the same 0.05% PHMB o/w emulsion was re-used 8 times revealed a drug delivery system activated by the presence of test bacteria.
Debridement and control of bacterial load are key-points of wound care. The aim of this study is to evaluate the effectiveness of autolytic debridement and management of bacterial load (bioburden) of an occlusive hydro-active dressing impregnated with polyhexamethylene biguanide (PHMB).
Polyhexamethylene biguanide (PHMB), an amphiphilic polymeric biocide, increased liver tumor incidence in male and female rats at 1000 and 1500 mg/l in drinking water, but not at 500 mg/l in previous studies. In another study, PHMB administered in diet at 4000 mg/kg was negative for hepatocellular tumors. The present studies evaluated bioavailability and distribution of PHMB administered in drinking water and diet and possible modes of action (MOA). PHMB in drinking water was unpalatable during the first 3 days, resulting in markedly decreased food consumption and decreased body weight. Ki-67 labeling index was increased in hepatocytes and endothelial cells dose responsively with PHMB administered in drinking water but not diet. Vitamin E had no effect on this. There was no cytotoxicity by histopathology or serum enzymes, and no increase in cytokines TNFα, IL-1α or NF-κB. Focal iron deposition in sinusoidal lining cells was detected. Microarray analyses were non-contributory. No effect on CAR or PPARα activation was detected. 14C-PHMB administered at 500, 1000, or 1500 mg/L in the drinking water or 4000 mg/kg in the diet was nearly completely absorbed and excreted in urine, with some fecal excretion. The hypothesized MOA for liver tumors induced by PHMB in drinking water is: 1) severe dehydration and starvation because of unpalatability, followed by ingestion with rapid absorption and urinary excretion; 2) increased hepatocyte proliferation; and 3) induction of hepatocellular foci and tumors. The PHMB-induced rat hepatocellular tumors are unlikely to pose a human cancer risk. However, the actual MOA has not been determined.
The bactericidal activities of polyhexamethylene biguanide hydrochloride (PHMB), 1-bromo-3-chloro-5,5-dimethylimidazolidine-2,4-dione (BCDMH), and the combination of the two (designated as PB) were compared using Escherichia coli as the test organism. PB exhibited strong bactericidal activity: 10 mg/L PHMB combined with 8 mg/L BCDMH resulted in approximately 5.74 log10 reduction (LR), whereby 320 mg/L PHMB or 20 mg/L BCDMH was about 5.53 and 6.56 LR, respectively. Analyses using scanning electron microscopy, flow cytometry, and atomic absorption spectroscopy indicated that PB, PHMB, and BCDMH disrupted cell membranes and changed membrane structure and permeability, resulting in the leakage of intracellular soluble proteins and ions. PB exerted stronger effects on potassium and magnesium leakage, membrane potential, and permeability than BCDMH did. PB caused less protein leakage than PHMB did. These results suggest that at a relatively low concentration, PB exhibited good bactericidal activity and physiological effect on E. coli.
A number of antimicrobial-impregnated discs to prevent central-line-associated bloodstream infection (CLABSI) are marketed but it is unclear which disc is most effective.
SAPO-11 nanosheets with partially filled micropores (N-SAPO-11) and a thickness of 10-20 nm were synthesized using polyhexamethylene biguanide hydrochloride (PHMB) as a mesoporogen and di-n-propylamine (DPA) as a microporous template. After Pt loading (0.5 wt%), the Pt/N-SAPO-11 catalyst exhibits higher selectivity for the isomers and lower selectivity for cracking products than conventional Pt/SAPO-11 catalysts in the hydroisomerization of n-dodecane.
In this study, three kinds of antiseptics which were 0.05% chlorhexidine, 0.2% polyhexamethylene biguanide (PHMB), or 200 ppm silver nanoparticle was introduced to incorporate in the sericin-based scaffold to produce the antimicrobial dressing for the treatment of infected chronic wound. The effects of antiseptic incorporation on the stability, release of sericin, and short-term and long-term (6 months) antimicrobial activity of the sericin dressing against gram-negative and gram-positive bacteria were investigated. We showed that the incorporation of each antiseptic did not have significant effect on the internal morphology (pore size ~ 73-105 μm), elasticity (Young’s modulus ~ 200-500 kPa), and the sericin release behavior of the sericin-based dressing. The release of sericin from the dressing was prolonged over 120 h and thereafter. Comparing among three antiseptics, 0.05% chlorhexidine incorporated in the sericin dressing showed the highest immediate and long-term (6 months) antimicrobial effect (largest inhibition zone) against most bacteria either gram-positive or gram-negative bacteria. The in vivo safety test following ISO10993 standard (Biological evaluation of medical devices - Part 6: Tests for local effects after implantation) confirmed that the sericin dressing incorporating 0.05% chlorhexidine did not irritate to tissue, comparing with the commercial material used generally in clinic (Allevyn(®), Smith & Nephew). We suggested the sericin dressing incorporating 0.05%chlorhexidine for the treatment of infected chronic wound. Chlorhexidine would reduce the risk of infection while the sericin may promote wound healing.
- Toxicology in vitro : an international journal published in association with BIBRA
- Published over 1 year ago
Polyhexamethylene biguanide (PHMB) is a member of the polymeric guanidine family, which is used as a biocide and preservative in industrial, medicinal, and consumer products. Some studies reported that polyhexamethylene guanidine phosphate, which is also a member of the guanidine family, induced severe inflammation and fibrosis in the lungs. However, limited studies have evaluated the pulmonary toxicity of PHMB associated with inflammatory responses. The aim of this study was to elucidate the inflammatory responses and its mechanisms induced by PHMB in lung cells. A549 cells exposed to PHMB showed decreased viability, reactive oxygen species (ROS) generation, inflammatory cytokine secretion, and nuclear factor kappa B (NF-κB) activation. The cells showed dose-dependent cytotoxicity and slight generation of ROS. PHMB triggered inflammatory cytokine secretion and NF-κB activation by modulating the degradation of IκB-α and the accumulation of nuclear p65. TNF-α plays important roles in IL-8 expression as well as NF-κB activation. Moreover, IL-8 production induced by PHMB was completely suppressed by a NF-κB inhibitor, but not by a ROS scavenger. In conclusion, we suggest that PHMB induces the inflammatory responses via the NF-κB signaling pathway.
Polyhexamethylene biguanide (PHMB)-based antiseptic solutions can reduce bacterial loads in different clinical settings and are believed to lower risk of infections.