title: Transdermal delivery of molecules is limited by full epidermis, not just stratum corneum.
abstract: OBJECTIVE
  Most methods to increase transdermal drug delivery focus on increasing stratum corneum permeability, without addressing the need to increase permeability of viable epidermis. Here, we assess the hypothesis that viable epidermis offers a significant permeability barrier that becomes rate limiting upon sufficient permeabilization of stratum corneum.
  
  
  METHODS
  We tested this hypothesis by using calibrated microdermabrasion to selectively remove stratum corneum or full epidermis in pig and human skin, and then measuring skin permeability to a small molecule (sulforhodamine) and macromolecules (bovine serum albumin, insulin, inactivated influenza vaccine) in vitro.
  
  
  RESULTS
  We found that removal of stratum corneum dramatically increased skin permeability to all compounds tested. However, removal of full epidermis increased skin permeability by another 1-2 orders of magnitude. We also studied the effects of removing skin tissue only from localized spots on the skin surface by covering skin with a mask containing 125-μm holes during tissue removal. Skin permeabilized in this less-invasive way showed similar results. This suggests that microdermabrasion of skin using a mask may provide an effective way to increase skin permeability.
  
  
  CONCLUSIONS
  We conclude that viable epidermis offers a significant permeability barrier that becomes rate limiting upon removal of stratum corneum.
authors.affiliation: Wallace Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA.
authors.forename: Samantha N
authors.initials: SN
authors.lastname: Andrews
authors.forename: Eunhye
authors.initials: E
authors.lastname: Jeong
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D003869:Dermabrasion; D004817:Epidermis / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007252:Influenza Vaccines / Q000493:pharmacokinetics*; D007328:Insulin / Q000493:pharmacokinetics*; D012235:Rhodamines / Q000493:pharmacokinetics*; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*; D012869:Skin Absorption; D013552:Swine
chemical_list: D007252:Influenza Vaccines; D007328:Insulin; D012235:Rhodamines; C022027:lissamine rhodamine B; D012710:Serum Albumin, Bovine