title: Electrically induced transport of macromolecules through oral buccal mucosa.
abstract: OBJECTIVE
  To investigate the feasibility of iontophoretic delivery of large molecules across buccal mucosa, and to establish its potential for enhanced drug delivery.
  
  
  METHODS
  Qualitative (6h) and quantitative (8 and 36 h) assessment of porcine buccal mucosa, using a diffusion cell in vitro model, was carried out by fluorescent microscopy and UV/Vis spectroscopy respectively, with four fluorescently-labeled model species (3 and 10 kDa dextrans, 12 kDa parvalbumin and 66 kDa bovine serum albumin, BSA). Passive and iontophoresis parameters were obtained. The experimental iontophoresis data were compared with theoretical predictions.
  
  
  RESULTS
  The two dextrans and parvalbumin showed enhanced permeation through buccal mucosa after anodal iontophoresis (1-6h). Passive diffusion and cathodal iontophoresis resulted in minimal permeation. BSA could not be measured by either mode. Iontophoretic delivery profiles compared to passive delivery, had reduced time lags (30-50 versus ~270 min) and increased flux (~37 times faster). Time lag factor/enhancement ratio (TLF/ER) data confirmed that iontophoresis significantly enhanced permeation. The diffusion coefficients (D, passive) for dextrans were significantly higher than for parvalbumin, with the converse obtained for solubility (C0); permeability coefficients (P) were similar for all three species. Potential differences (V) for the two higher kDa species were significantly higher than for the lowest kDa species. Experimental and theoretical data were in reasonable agreement.
  
  
  CONCLUSIONS
  The experimental and theoretical data, confirming enhanced delivery of the model species via iontophoresis, gave a suitable basis for its potential application in the mouth, in a clinical setting and opens pathways to further research for delivering precious drugs topically and systemically.
authors.affiliation: Oral Growth and Development (Dental Physical Sciences), Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, United Kingdom. m.patel@qmul.ac.uk
authors.forename: Mangala P
authors.initials: MP
authors.lastname: Patel
authors.forename: Svetla T
authors.initials: ST
authors.lastname: Churchman
authors.forename: Alan T
authors.initials: AT
authors.lastname: Cruchley
authors.forename: Michael
authors.initials: M
authors.lastname: Braden
authors.forename: David M
authors.initials: DM
authors.lastname: Williams
mesh_terms: D000418:Albumins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D003911:Dextrans / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D005240:Feasibility Studies; D019793:Fluorescein; D005456:Fluorescent Dyes; D007478:Iontophoresis / Q000379:methods*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008956:Models, Chemical; D008970:Molecular Weight; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism; D010320:Parvalbumins / Q000008:administration & dosage / Q000493:pharmacokinetics; D010539:Permeability; D012235:Rhodamines; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000493:pharmacokinetics; D012995:Solubility; D013552:Swine; D013997:Time Factors
chemical_list: D000418:Albumins; D003911:Dextrans; D005456:Fluorescent Dyes; C067661:Fluoro-Ruby; D010320:Parvalbumins; D012235:Rhodamines; D012710:Serum Albumin, Bovine; C005358:tetramethylrhodamine; D019793:Fluorescein