title: Human nail plate modifications induced by onychomycosis: implications for topical therapy.
abstract: OBJECTIVE
  Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations.
  
  
  METHODS
  The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail's density was determined via pycnometry and the nail's ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying water and rhodamine uptake.
  
  
  RESULTS
  Chronic in vivo nail plate infection increased human nailplate thickness (healthy 0.49 ± 0.15 mm; diseased 1.20 ± 0.67 mm), but reduced its tensile strength (healthy 63.7 ± 13.4 MPa; diseased 41.7 ± 5.0 MPa) and density (healthy 1.34 ± 0.01 g/cm(3); diseased 1.29 ± 0.00 g/cm(3)). Onchomycosis caused cell-cell separation, without disrupting the nail disulfide bonds or desmosomes. The diseased and healthy nails showed equivalent water uptake profiles, but the rhodamine penetration was 4-fold higher in the diseased nails using a PBS vehicle and 3 -fold higher in an ethanol/PBS vehicle.
  
  
  CONCLUSIONS
  Onchomycotic nails presented a thicker but more porous barrier, and its eroded intracellular matrix rendered the tissue more permeable to topically applied chemicals when an aqueous vehicle was used.
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29 -39 Brunswick Square, London, WC1N 1AX, UK.
authors.forename: A
authors.initials: A
authors.lastname: Baraldi
authors.forename: S A
authors.initials: SA
authors.lastname: Jones
authors.forename: S
authors.initials: S
authors.lastname: Guesné
authors.forename: M J
authors.initials: MJ
authors.lastname: Traynor
authors.forename: W J
authors.initials: WJ
authors.lastname: McAuley
authors.forename: M B
authors.initials: MB
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Murdan
mesh_terms: D000287:Administration, Topical; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics; D005533:Foot Dermatoses / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009262:Nails / Q000737:chemistry / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D014009:Onychomycosis / Q000378:metabolism / Q000473:pathology*; D010539:Permeability; D012235:Rhodamines / Q000008:administration & dosage / Q000493:pharmacokinetics; D013718:Tensile Strength
chemical_list: D005456:Fluorescent Dyes; D012235:Rhodamines