1887

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.

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2016-08-01
2019-10-22
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References

  1. APVMA ( 2011;) Polihexanide Carcinogenicity: Analysis of Human Health Risk. Symondston, Australia:: Australian Pesticides and Veterinary Medicines Authority;.
    [Google Scholar]
  2. Broxton P. , Woodcock P. M. , Gilbert P. . ( 1983;). A study of the antibacterial activity of some polyhexamethylene biguanides towards Escherichia coli ATCC 8739. . J Appl Bacteriol 54: 345–353. [CrossRef] [PubMed]
    [Google Scholar]
  3. Broxton P. , Woodcock P. M. , Heatley F. , Gilbert P. . ( 1984a;). Interaction of some polyhexamethylene biguanides and membrane phospholipids in Escherichia coli . . J Appl Bacteriol 57: 115–124. [CrossRef] [PubMed]
    [Google Scholar]
  4. Broxton P. , Woodcock P. M. , Gilbert P. . ( 1984b;). Binding of some polyhexamethylene biguanides to the cell envelope of Escherichia coli ATCC 8739. . Microbios 41: 15–22.
    [Google Scholar]
  5. Broxton P. , Woodcock P. M. , Gilbert P. . ( 1984c;). Injury and recovery of Escherichia coli ATCC 8739 from treatment with some polyhexamethylene biguanides. . Microbios 40: 187–193.
    [Google Scholar]
  6. Burger R. M. , Franco R. J. , Drlica K. . ( 1994;). Killing acanthamoebae with polyaminopropyl biguanide: quantitation and kinetics. . Antimicrob Agents Chemother 38: 886–888. [CrossRef] [PubMed]
    [Google Scholar]
  7. Cano-Parra J. , Bueno-Gimeno I. , Lainez B. , Córdoba J. , Montés-Micó R. . ( 1999;). Antibacterial and antifungal effects of soft contact lens disinfection solutions. . Cont Lens Anterior Eye 22: 83–86. [CrossRef] [PubMed]
    [Google Scholar]
  8. Chadeau E. , Dumas E. , Adt I. , Degraeve P. , Noël C. , Girodet C. , Oulahal N. . ( 2012;). Assessment of the mode of action of polyhexamethylene biguanide against Listeria innocua by Fourier transformed infrared spectroscopy and fluorescence anisotropy analysis. . Can J Microbiol 58: 1353–1361. [CrossRef] [PubMed]
    [Google Scholar]
  9. Chang J. M. , McCanna D. J. , Subbaraman L. N. , Jones L. W. . ( 2015;). Efficacy of antimicrobials against biofilms of Achromobacter and Pseudomonas . . Optom Vis Sci 92: 506–513. [CrossRef] [PubMed]
    [Google Scholar]
  10. Chindera K. , Mahato M. , Sharma A. K. , Horsley H. , Kloc-Muniak K. , Kamaruzzaman N. F. , Kumar S. , McFarlane A. , Stach J. et al. ( 2016;). The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes. . Sci Rep 6: 23121. [CrossRef] [PubMed]
    [Google Scholar]
  11. Choy C. K. , Cho P. , Boost M. V. . ( 2013;). Cytotoxicity of rigid gas-permeable lens care solutions. . Clin Exp Optom 96: 467–471. [CrossRef] [PubMed]
    [Google Scholar]
  12. Clapp M. J. L. , Iswaran T. J. , Major P. . ( 1977a;). Polyhexamethylene Biguanide: 80-Week Skin Painting Study in Mice. Report No. Ctl/P/331. Macclesfield, UK:: Central Toxicology Laboratory;.
    [Google Scholar]
  13. Clapp M. J. L. , Iswaran T. J. , Rowson S. M. , Major T. M. . ( 1977b;). Polyhexamethylene Biguanide: Life-time Feeding Study in the Mouse. Report No. Ctl/P/332. Macclesfield, UK:: Central Toxicology Laboratory;.
    [Google Scholar]
  14. Creppy E. E. , Diallo A. , Moukha S. , Eklu-Gadegbeku C. , Cros D. . ( 2014;). Study of epigenetic properties of poly(hexamethylene biguanide) hydrochloride (PHMB). . Int J Environ Res Public Health 11: 8069–8092. [CrossRef] [PubMed]
    [Google Scholar]
  15. DIN ( 2009;). EN 58940-7:2009-08 - Medical microbiology. Susceptibility testing of microbial pathogens to antimicrobial agents - Part 7: Determination of the minimum bactericidal concentration (MBC) with the method of microbouillon dilution. (Text in German and English). .
  16. DIN ( 2012;). EN 13727:2012+A1:2013 - Chemical disinfectants and antiseptics. Quantitative suspension test for the evaluation of bactericidal activity in the medical area – (Test method and requirements (phase 2, step 1) (German version). .
  17. ECHA/RAC ( 2011;). Opinion proposing harmonised classification and labelling at community level of polyhexamethylene biguanide or poly(hexamethylene) biguanidehydrochloride or PHMB. Helsinki, Finland:: European Chemicals Agency;.
    [Google Scholar]
  18. Eberlein T. , Haemmerle G. , Signer M. , Gruber Moesenbacher U. , Traber J. , Mittlboeck M. , Abel M. , Ztrohal R. . ( 2012;). Comparison of PHMB-containing dressing and silver dressings in patients with critically colonised or locally infected wounds. . J Wound Care 21: 12. [CrossRef] [PubMed]
    [Google Scholar]
  19. ECHA/ANSES ( 2013;). CLH Report for PHMB CAS 27083-27-8 or 32289-58-0. Helsinki, Finland:: European Chemicals Agency;.
    [Google Scholar]
  20. Gilbert P. , Moore L. E. . ( 2005;). Cationic antiseptics: diversity of action under a common epithet. . J Appl Microbiol 99: 703–715. [CrossRef] [PubMed]
    [Google Scholar]
  21. Gottrup F. , Apelqvist J. , Bjarnsholt T. , Bjansholt T. , Cooper R. , Moore Z. , Peters E. J. , Probst S. . ( 2013;). EWMA document: antimicrobials and non-healing wounds. Evidence, controversies and suggestions. . J Wound Care 22: S1–89. [CrossRef] [PubMed]
    [Google Scholar]
  22. Heyer K. , Augustin M. , Protz K. , Herberger K. , Spehr C. , Rustenbach S. J. . ( 2013;). Effectiveness of advanced versus conventional wound dressings on healing of chronic wounds: systematic review and meta-analysis. . Dermatology 226: 172–184. [CrossRef] [PubMed]
    [Google Scholar]
  23. Hübner N. O. , Kramer A. . ( 2010;). Review on the efficacy, safety and clinical applications of polihexanide, a modern wound antiseptic. . Skin Pharmacol Physiol 23: 17–27. [CrossRef] [PubMed]
    [Google Scholar]
  24. Ikeda T. , Tazuke S. , Watanabe M. . ( 1983;). Interaction of biologically active molecules with phospholipid membranes. I. Fluorescence depolarization studies on the effect of polymeric biocide bearing biguanide groups in the main chain. . Biochim Biophys Acta 735: 380–386.[PubMed] [CrossRef]
    [Google Scholar]
  25. Ikeda T. , Tazuke S. , Bamford C. H. . ( 1985a;). Interaction of membrane active biguanides with negatively charged species. A model for their interaction with target sites in microbial membranes. . J Chem Res 6: 180–181.
    [Google Scholar]
  26. Ikeda T. , Tazuke S. , Bamford C. H. , Ledwith A. . ( 1985b;). Spectroscopic studies on the interaction of polymeric in-chain biguanide biocide with phospholipid membranes as probed by 8-anilinonaphthalene-1-sulfonate. . Bull Chem Soc Jpn 58: 705–709. [CrossRef]
    [Google Scholar]
  27. ISO ( 2009;). EN 10993-5:2009 - Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity (ISO 10993-5:2009). (German version). Geneva, Switzerland:: International Organization for Standardization;.
    [Google Scholar]
  28. ISO ( 2012;). prEN 20743:2012 - Textiles - Determination of antibacterial activity of textile products (ISO/DIS 20743:2012). ( German version). Geneva, Switzerland:: International Organization for Standardization;.
    [Google Scholar]
  29. Kaehn K. . ( 2010;). Polihexanide: a safe and highly effective biocide. . Skin Pharmacol Physiol 23: 7–16. [CrossRef] [PubMed]
    [Google Scholar]
  30. Kapalschinski N. , Seipp H. M. , Onderdonk A. B. , Goertz O. , Daigeler A. , Lahmer A. , Lehnhardt M. , Hirsch T. . ( 2013;). Albumin reduces the antibacterial activity of polyhexanide-biguanide-based antiseptics against Staphylococcus aureus and MRSA. . Burns 39: 1221–1225. [CrossRef] [PubMed]
    [Google Scholar]
  31. Leysen J. , Goossens A. , Lambert J. , Aerts O. . ( 2014;). Polyhexamethylene biguanide is a relevant sensitizer in wet wipes. . Contact Dermatitis 70: 323–325. [CrossRef] [PubMed]
    [Google Scholar]
  32. Libby G. , Donnelly L. A. , Donnan P. T. , Alessi D. R. , Morris A. D. , Evans J. M. . ( 2009;). New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. . Diabetes Care 32: 1620–1625. [CrossRef] [PubMed]
    [Google Scholar]
  33. Lipsky B. A. , Hoey C. . ( 2009;). Topical antimicrobial therapy for treating chronic wounds. . Clin Infect Dis 49: 1541–1549. [CrossRef] [PubMed]
    [Google Scholar]
  34. Lui A. C. , Netto A. L. , Silva C. B. , Hida R. , Mendes T. S. , Lui G. A. , Gemperli D. B. , Vital E. D. . ( 2009;). Antimicrobial efficacy assessment of multi-use solution to disinfect hydrophilic contact lens, in vitro. . Arq Bras Oftalmol 72: 626–630.[PubMed] [CrossRef]
    [Google Scholar]
  35. Milburn G. M. . ( 1996;). Polyhexamethylene Biguanide: Two Year Oncogenic Study in Mice. Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK. Report No. Ctl/P/4649. Macclesfield, UK:: Central Toxicology Laboratory;.
    [Google Scholar]
  36. Müller G. , Kramer A. . ( 2008;). Biocompatibility index of antiseptic agents by parallel assessment of antimicrobial activity and cellular cytotoxicity. . J Antimicrob Chemother 61: 1281–1287. [CrossRef] [PubMed]
    [Google Scholar]
  37. Reindel W. , Merchea M. M. , Rah M. J. , Zhang L. . ( 2013;). Meta-analysis of the ocular biocompatibility of a new multipurpose lens care system. . Clin Ophthalmol 7: 2051–2056. [CrossRef] [PubMed]
    [Google Scholar]
  38. SCCS ( 2014;). Opinion on the Safety of Poly(hexamethylene) Biguanide Hydrochloride or Polyaminopropyl Biguanide (PHMB) in Cosmetic Products. SCCS/1535/14. Revision Of 16. Brussels, Belgium:: Scientific Committee on Consumer Safety;.
    [Google Scholar]
  39. Souza A. L. , Ceridório L. F. , Paula G. F. , Mattoso L. H. , Oliveira O. N. . ( 2015;). Understanding the biocide action of poly (hexamethylene biguanide) using Langmuir monolayers of dipalmitoyl phosphatidylglycerol. . Colloids Surf B Biointerfaces 132: 117–121. [CrossRef] [PubMed]
    [Google Scholar]
  40. Sutton S. V. , Franco R. J. , Porter D. A. , Mowrey-McKee M. F. , Busschaert S. C. , Hamberger J. F. , Proud D. W. . ( 1991;). D-value determinations are an inappropriate measure of disinfecting activity of common contact lens disinfecting solutions. . Appl Environ Microbiol 57: 2021–2026.[PubMed]
    [Google Scholar]
  41. Sütterlin S. , Tano E. , Bergsten A. , Tallberg A. B. , Melhus A. . ( 2012;). Effects of silver-based wound dressings on the bacterial flora in chronic leg ulcers and its susceptibility in vitro to silver. . Acta Derm Venereol 92: 34–39. [CrossRef] [PubMed]
    [Google Scholar]
  42. Wessels S. , Ingmer H. . ( 2013;). Modes of action of three disinfectant active substances: a review. . Regul Toxicol Pharmacol 67: 456–467. [CrossRef] [PubMed]
    [Google Scholar]
  43. Wiegand C. , Heinze T. , Hipler U.-C. . ( 2009;). Comparative in vitro study on cytotoxicity, antimicrobial activity, and binding capacity for pathophysiological factors in chronic wounds of alginate and silver-containing alginate. . Wound Repair Regen 17: 511–521. [CrossRef] [PubMed]
    [Google Scholar]
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