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Current Microbiology

, Volume 66, Issue 3, pp 271–278 | Cite as

Production and Evaluation of an Antimicrobial Peptide-Containing Wafer Formulation for Topical Application

  • Noelle H. O’Driscoll
  • Olga Labovitiadi
  • T. P. Tim Cushnie
  • Kerr H. Matthews
  • Derry K. Mercer
  • Andrew J. Lamb
Article

Abstract

A targeted approach for direct topical antimicrobial delivery involving the formulation of impregnated freeze-dried wafers prepared from a natural polymer has been assessed to consider potential for treatment of wounded skin. The synthetic cationic antimicrobial peptides (CAPs) NP101 and NP108 were found to have modest in vitro activity against bacterial species commonly associated with wound infections. Minimum inhibitory concentration/minimum bactericidal concentrations against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were found to be 0.31 mg/ml for NP101 and 0.25–0.5 mg/ml for NP108. Rapid, substantial cytoplasmic potassium loss was induced by NP108 in E. coli, but not the other species. Through scanning electron microscopy, both CAPs were observed to alter cell morphology, prevent normal septation, promote cell aggregation and trigger release or formation of extracellular filaments. Wafers harbouring these agents displayed substantial antibacterial activity when assessed by standard diffusion assay. These data confirm that topical delivery of CAPs, through their incorporation within freeze-dried wafer formulations prepared from natural polymers, represents a potential viable approach for treating skin infection.

Keywords

Chronic Wound Topical Delivery Intracellular Potassium Potassium Loss Cationic Antimicrobial Peptide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors would like to thank Emily Hunter and Iain Tough for assistance with operation of the SEM and Dr Tim King for valuable assistance with interpretation of SEM images. The work was supported in part by an award (G08/10) to KHM by Tenovus Scotland. The authors declare that they have no conflict of interest.

Supplementary material

284_2012_268_MOESM1_ESM.doc (2.1 mb)
Supplementary material 1 (DOC 2140 kb)
284_2012_268_MOESM2_ESM.doc (2.6 mb)
Supplementary material 2 (DOC 2634 kb)

References

  1. 1.
    Aucken H, Ganner M, Murchan S, Cookson B, Johnson A (2002) A new UK strain of epidemic methicillin-resistant Staphylococcus aureus (EMRSA-17) resistant to multiple antibiotics. J Antimicrob Chemother 50:171–175. doi: 10.1093/jac/dkf117 PubMedCrossRefGoogle Scholar
  2. 2.
    Bhat S, Milner S (2007) Antimicrobial peptides in burns and wounds. Curr Protein Pept Sci 8:506–520PubMedCrossRefGoogle Scholar
  3. 3.
    Boateng JS, Matthews KH, Auffret AD, Humphrey MJ, Stevens HN, Eccleston GM (2009) In vitro drug release studies of polymeric freeze-dried wafers and solvent-cast films using paracetamol as a model soluble drug. Int J Pharm 378:66–72. doi: 10.1016/j.ijpharm.2009.05.038 PubMedCrossRefGoogle Scholar
  4. 4.
    Boateng JS, Auffret AD, Matthews KH, Humphrey MJ, Stevens HNE, Eccleston GM (2010) Characterisation of freeze-dried wafers and solvent evaporated films as potential drug delivery systems to mucosal surfaces. Int J Pharm 389:24–31. doi: 10.1016/j.ijpharm.2010.01.008 PubMedCrossRefGoogle Scholar
  5. 5.
    Chua K, Laurent F, Coombs G, Grayson ML, Howden BP (2011) Not community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)! A clinician’s guide to community MRSA—its evolving antimicrobial resistance and implications for therapy. Clin Infect Dis 52:99–114. doi: 10.1093/cid/ciq067 PubMedCrossRefGoogle Scholar
  6. 6.
    Deming TJ (2007) Synthetic polypeptides for biomedical applications. Prog Polym Sci 32:858–875. doi: 10.1016/j.progpolymsci.2007.05.010 CrossRefGoogle Scholar
  7. 7.
    Fonder MA, Lazarus GS, Cowan DA, Aronson-Cook B, Kohli AR, Mamelak AJ (2008) Treating the chronic wound: a practical approach to the care of nonhealing wounds and wound care dressings. J Am Acad Dermatol 58:185–206PubMedCrossRefGoogle Scholar
  8. 8.
    Hale JDF, Hancock REW (2007) Alternative mechanisms of action of cationic antimicrobial peptides on bacteria. Expert Rev Anti Infect Ther 10:951–959. doi: 10.1586/14787210.5.6.961 CrossRefGoogle Scholar
  9. 9.
    Hancock RE, Sahl HG (2006) Antimicrobial and host-defence peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24:1551–1557. doi: 10.1038/nbt1267 PubMedCrossRefGoogle Scholar
  10. 10.
    Lambert PA, Hammond SM (1973) Potassium fluxes, first indications of membrane damage in micro-organisms. Biochem Biophys Res Commun 54:796–799. doi: 10.1016/0006-291X(73)91494-0 PubMedCrossRefGoogle Scholar
  11. 11.
    Lu H, Tonge PJ (2010) Drug–target residence time: critical information for lead optimization. Curr Opin Chem Biol 14:467–474. doi: 10.1016/j.cbpa.2010.06.176 PubMedCrossRefGoogle Scholar
  12. 12.
    Malmsten M, Kasetty G, Pasupuleti M, Alenfall J, Schmodtchen A (2011) Highly selective end-tagged antimicrobial peptides derived from PRELP. PLoS ONE 6:e16400. doi: 10.1371/journal.pone.0016400 PubMedCrossRefGoogle Scholar
  13. 13.
    Martin N, Dodds C (2006) Protective mechanisms of the body. Anaesth Intensive Care Med 7:459–461. doi: 10.1053/j.mpaic.2006.09.008 CrossRefGoogle Scholar
  14. 14.
    Matthews KH, Stevens HNE, Auffret AD, Humphrey MJ, Eccleston GM (2005) Lyophilised wafers as a drug delivery system for wound healing containing methylcellulose as a viscosity modifier. Int J Pharm 289:51–62. doi: 10.1016/j.ijpharm.2004.10.022 PubMedCrossRefGoogle Scholar
  15. 15.
    Matthews KH, Stevens HNE, Auffret AD, Humphrey MJ, Eccleston GM (2008) Formulation, stability and thermal analysis of lyophilised wound healing wafers containing an insoluble MMP-3 inhibitor and a non-ionic surfactant. Int J Pharm 356:110–120. doi: 10.1016/j.ijpharm.2007.12.043 PubMedCrossRefGoogle Scholar
  16. 16.
    O’Neil D, Mercer D, Charrier C (2006) Inhibition of biofilm organisms. International Patent A61K 38/04Google Scholar
  17. 17.
    Pag U, Oedenkoven M, Sass V, Shai Y, Shamova O, Antcheva N, Tossi A, Sahl HG (2008) Analysis of in vitro activities and models of action of synthetic antimicrobial peptides derived from an alpha-helical ‘sequence template’. J Antimicrob Chemother 61:341–352. doi: 10.1093/jac/dkm479 PubMedCrossRefGoogle Scholar
  18. 18.
    Pereira HA (2006) Novel therapies based on cationic antimicrobial peptides. Curr Pharm Biotechnol 7:229–234. doi: 10.2174/138920106777950771 PubMedCrossRefGoogle Scholar
  19. 19.
    Reddy KVR, Yedery RD, Aranha C (2004) Antimicrobial peptides: premises and promises. Int J Antimicrob Agents 24:536–547. doi: 10.1016/j.ijantimicag.2004.09.005 PubMedCrossRefGoogle Scholar
  20. 20.
    Schauber J, Gallo RL (2008) Antimicrobial peptides and the skin immune defence system. J Allergy Clin Immunol 122:261–266. doi: 10.1016/j.jaci.2008.03.027 PubMedCrossRefGoogle Scholar
  21. 21.
    Shukla A, Fleming KE, Chuang HF, Chau TM, Loose CR, Stephanopoulos GN, Hammond PT (2010) Controlling the release of peptide antimicrobial agents from surfaces. Biomaterials 31:2348–2357. doi: 10.1016/j.biomaterials.2009.11.082 PubMedCrossRefGoogle Scholar
  22. 22.
    Steinberg DA, Hurst MA, Fujii CA, Kung AH, Ho JF, Cheng FC, Loury DJ, Fiddes JC (1997) Protegrin-1: a broad-spectrum, rapidly microbicidal peptide with in vivo activity. Antimicrob Agents Chemother 41:1738–1742PubMedGoogle Scholar
  23. 23.
    Stephens PJ (2011) Dysfunctional wound healing in chronic wounds. In: Farrar D (ed) Advanced wound repair therapies. Woodhead Publishing Limited, Cambridge, pp 3–23CrossRefGoogle Scholar
  24. 24.
    Superti F, Ammendolia M, Marchetti M (2008) New advances in anti-HSV chemotherapy. Curr Med Chem 15:900–911. doi: 10.2174/092986708783955419 PubMedCrossRefGoogle Scholar
  25. 25.
    Supp DM, Neely AN (2008) Cutaneous antimicrobial gene therapy: engineering human skin replacements to combat wound infection. Expert Rev Dermatol 3:73–84. doi: 10.1586/17469872.3.1.73 CrossRefGoogle Scholar
  26. 26.
    Tenover FC, Goering RV (2009) Methicillin-resistant Staphylococcus aureus strain USA300: origin and epidemiology. J Antimicrob Chemother 64:441–446. doi: 10.1093/jac/dkp241 PubMedCrossRefGoogle Scholar
  27. 27.
    Wild T, Rahbarnia A, Kellner M, Sobotka L, Eberlein T (2010) Basics in nutrition and wound healing. Nutrition 26:862–866. doi: 10.1016/j.nut.2010.05.008 PubMedCrossRefGoogle Scholar
  28. 28.
    Zaiou M (2007) Multifunctional antimicrobial peptides: therapeutic targets in several human diseases. J Mol Med 85:317–329. doi: 10.1007/s00109-006-0143-4 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Noelle H. O’Driscoll
    • 1
  • Olga Labovitiadi
    • 2
  • T. P. Tim Cushnie
    • 3
  • Kerr H. Matthews
    • 1
  • Derry K. Mercer
    • 4
  • Andrew J. Lamb
    • 1
  1. 1.School of Pharmacy and Life Sciences, Research Institute for Health and WelfareRobert Gordon UniversityAberdeenUK
  2. 2.School of ScienceUniversity of Greenwich, Medway CampusChatham MaritimeUK
  3. 3.Faculty of MedicineMahasarakham UniversityKantarawichaiThailand
  4. 4.NovaBiotics Ltd.AberdeenUK

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