title: Distribution and visualisation of chlorhexidine within the skin using ToF-SIMS: a potential platform for the design of more efficacious skin antiseptic formulations.
abstract: OBJECTIVE
  In order to increase the efficacy of a topically applied antimicrobial compound the permeation profile, localisation and mechanism of action within the skin must first be investigated.
  
  
  METHODS
  Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to visualise the distribution of a conventional antimicrobial compound, chlorhexidine digluconate, within porcine skin without the need for laborious preparation, radio-labels or fluorescent tags.
  
  
  RESULTS
  High mass resolution and high spatial resolution mass spectra and chemical images were achieved when analysing chlorhexidine digluconate treated cryo-sectioned porcine skin sections by ToF-SIMS. The distribution of chlorhexidine digluconate was mapped throughout the skin sections and our studies indicate that the compound appears to be localised within the stratum corneum. In parallel, tape strips taken from chlorhexidine digluconate treated porcine skin were analysed by ToF-SIMS to support the distribution profile obtained from the skin sections.
  
  
  CONCLUSIONS
  ToF-SIMS can act as a powerful complementary technique to map the distribution of topically applied compounds within the skin.
authors: School of Pharmacy, Keele University, Keele, Staffordshire ST5 5BG, UK. a.m.judd@keele.ac.uk
authors: Amy M
authors: AM
authors: Judd
authors: David J
authors: DJ
authors: Scurr
authors: Jon R
authors: JR
authors: Heylings
authors: Ka-Wai
authors: KW
authors: Wan
authors: Gary P
authors: GP
authors: Moss
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000493:pharmacokinetics*; D002710:Chlorhexidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods; D013552:Swine
chemical_list: D000891:Anti-Infective Agents, Local; C010882:chlorhexidine gluconate; D002710:Chlorhexidine
references: Pharm Res. 1993 Oct;10(10):1500-6
references: 8272414
references: Skin Pharmacol. 1996;9(1):69-77
references: 8868035
references: Eur J Pharm Biopharm. 2004 Sep;58(2):301-16
references: 15296957
references: Toxicol In Vitro. 1994 Aug;8(4):665-7
references: 20692983
references: J Infect Dis. 1989 Oct;160(4):644-50
references: 2794559
references: Curr Opin Infect Dis. 2003 Apr;16(2):103-24
references: 12734443
references: Exp Dermatol. 2000 Jun;9(3):165-9
references: 10839713
references: Genome Res. 2008 Jul;18(7):1043-50
references: 18502944
references: Skin Res Technol. 2007 Aug;13(3):242-51
references: 17610645
references: J Invest Dermatol. 2005 Aug;125(2):183-200
references: 16098026
references: Clin Infect Dis. 2008 Jan 15;46(2):274-81
references: 18171263
references: Int J Pharm. 2007 Aug 1;340(1-2):71-5
references: 17467206
references: Biochim Biophys Acta. 2006 Jul;1758(7):923-33
references: 16730643
references: J Invest Dermatol. 1959 Jan;32(1):49-59
references: 13620967
references: Antimicrob Agents Chemother. 2008 Oct;52(10):3633-6
references: 18676882
references: Int J Pharm. 2000 Dec 4;210(1-2):69-82
references: 11163989
references: Pharm Res. 2001 Oct;18(10):1472-5
references: 11697475
references: Br Med J. 1972 Jan 15;1(5793):136-40
references: 5007838
references: Mol Pharm. 2011 Jun 6;8(3):969-75
references: 21548600
references: J Biomed Opt. 2003 Oct;8(4):601-7
references: 14563197
references: Br J Dermatol. 1980 Mar;102(3):267-75
references: 7370175
references: Rapid Commun Mass Spectrom. 2004;18(24):3051-60
references: 15543527
references: Skin Res Technol. 2005 May;11(2):97-101
references: 15807806
references: Toxicol In Vitro. 2004 Jun;18(3):351-8
references: 15046783
references: Annu Rev Microbiol. 1988;42:441-64
references: 3144238
references: J Control Release. 1998 Dec 4;56(1-3):7-21
references: 9801425
references: Br J Pharmacol Chemother. 1954 Jun;9(2):192-6
references: 13172429
references: Arch Dermatol Res. 1997 Aug;289(9):514-8
references: 9341971
references: Science. 2008 Dec 19;322(5909):1857-61
references: 19095943
references: J Lipid Res. 1983 Feb;24(2):120-30
references: 6833889
references: Histochem Cell Biol. 2008 Sep;130(3):421-34
references: 18618129
references: J Invest Dermatol. 2007 May;127(5):1205-9
references: 17218938
references: J Proteome Res. 2006 Nov;5(11):2889-900
references: 17081040
references: Pharm Res. 2009 Feb;26(2):316-28
references: 18941872
references: Int J Cosmet Sci. 2012 Dec;34(6):551-9
references: 22957937
references: Mol Cell Proteomics. 2011 Mar;10(3):M110.005991
references: 21149303
references: Antimicrob Agents Chemother. 2003 Jun;47(6):1988-90
references: 12760881
references: Skin Pharmacol Appl Skin Physiol. 2003 Jul-Aug;16(4):217-27
references: 12784061