title: In vivo, in situ imaging of microneedle insertion into the skin of human volunteers using optical coherence tomography.
abstract: OBJECTIVE
  To gather sub-surface in situ images of microneedle-treated human skin, in vivo, using optical coherence tomography (OCT). This is the first study to utilise OCT to investigate the architectural changes that are induced in skin following microneedle application.
  
  
  METHODS
  Steel, silicon and polymer microneedle devices, with different microneedle arrangements and morphologies, were applied to two anatomical sites in human volunteers following appropriate ethical approval. A state-of-the-art ultrahigh resolution OCT imaging system operating at 800 nm wavelength and <3 µm effective axial resolution was used to visualise the microneedle-treated area during insertion and/or following removal of the device, without any tissue processing.
  
  
  RESULTS
  Transverse images of a microneedle device, in situ, were captured by the OCT system and suggest that the stratified skin tissue is compressed during microneedle application. Following removal of the device, the created microchannels collapse within the in vivo environment and, therefore, for all studied devices, microconduit dimensions are markedly smaller than the microneedle dimensions.
  
  
  CONCLUSIONS
  Microchannels created in the upper skin layers by microneedles are less invasive than previous histology predicts. OCT has the potential to play a highly influential role in the future development of microneedle devices and other transdermal delivery systems.
authors.affiliation: Gene Delivery Research Group, Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3NB, UK. coulmansa@cardiff.ac.uk
authors.forename: Siôn A
authors.initials: SA
authors.lastname: Coulman
authors.forename: James C
authors.initials: JC
authors.lastname: Birchall
authors.forename: Aneesh
authors.initials: A
authors.lastname: Alex
authors.forename: Marc
authors.initials: M
authors.lastname: Pearton
authors.forename: Bernd
authors.initials: B
authors.lastname: Hofer
authors.forename: Conor
authors.initials: C
authors.lastname: O'Mahony
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Drexler
authors.forename: Boris
authors.initials: B
authors.lastname: Považay
mesh_terms: D000328:Adult; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D006801:Humans; D007271:Injections, Intradermal; D008297:Male; D008845:Microinjections / Q000295:instrumentation / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D009339:Needles; D012867:Skin / Q000378:metabolism / Q000648:ultrastructure*; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D041623:Tomography, Optical Coherence; D055815:Young Adult
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