title: Transdermal macromolecular delivery: real-time visualization of iontophoretic and chemically enhanced transport using two-photon excitation microscopy.
abstract: OBJECTIVE
  To investigate the transdermal delivery of a model macromolecule by passive and iontophoretic means following pretreatment with C12-penetration enhancers and to visualise transport across human stratum corneum (SC) in real time.
  
  
  METHODS
  Transport studies of dextran, labelled with fluorescent Cascade Blue (D-CB: M(R) = 3 kDa) across human stratum corneum, were conducted during passive and iontophoretic modes of delivery following pretreatment with either dodecyltrimethylammonium bromide (DTAB), sodium dodecyl sulphate (SDS) or Azone. Size-exclusion chromatography was used to assess maintenance of dextran structural integrity throughout experimental lifetime. Two-photon excitation microscopy was employed to visualise real-time dextran transport during current application.
  
  
  RESULTS
  The positively charged C12-enhancer DTAB elevated passive D-CB steady-state flux (J(ss)) and was the only enhancer to do so above control during iontophoresis. The negatively charged SDS had the least effect during both stages. On-line macromolecular transport was visualised, indicating both inter- and intra-cellular pathways across SC during current application. No transport was visible across untreated SC during passive transport.
  
  
  CONCLUSIONS
  Use of a positively charged enhancer may improve J(ss) of anionic macromolecular penetrants during passive and iontophoretic delivery. On-line visualisation of iontophoresis across SC was possible and can provide mechanistic insight into SC transport pathways.
authors.affiliation: Pharmaceutical Sciences Research Institute, Aston Pharmacy School, Aston University, Birmingham, UK.
authors.forename: B S
authors.initials: BS
authors.lastname: Grewal
authors.forename: A
authors.initials: A
authors.lastname: Naik
authors.forename: W J
authors.initials: WJ
authors.lastname: Irwin
authors.forename: G
authors.initials: G
authors.lastname: Gooris
authors.forename: C J
authors.initials: CJ
authors.lastname: de Grauw
authors.forename: H G
authors.initials: HG
authors.lastname: Gerritsen
authors.forename: J A
authors.initials: JA
authors.lastname: Bouwstra
mesh_terms: D000279:Administration, Cutaneous; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics; D001381:Azepines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003911:Dextrans / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007478:Iontophoresis / Q000379:methods*; D008856:Microscopy, Fluorescence / Q000379:methods; D017785:Photons; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000502:physiology*; D012967:Sodium Dodecyl Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D001381:Azepines; D003911:Dextrans; D005456:Fluorescent Dyes; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; C013912:decyltrimethylammonium; C035229:laurocapram; D012967:Sodium Dodecyl Sulfate