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Transdermal Delivery of Molecules is Limited by Full Epidermis, Not Just Stratum Corneum



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.


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.


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.


We conclude that viable epidermis offers a significant permeability barrier that becomes rate limiting upon removal of stratum corneum.

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We would like to thank Dr. Yeu-Chun Kim for supplying and preparing the fluorescently labeled influenza virus; Dr. Jeong-Woo Lee and Aritra Sengupta for advice on the sulforhodamine diffusion experiments; and Donna Bondy for administrative support. This work was carried out in the Center for Drug Design, Development and Delivery and the Institute for Bioengineering and Bioscience at Georgia Tech with financial support in part from the National Institutes of Health. Mark Prausnitz serves as a consultant and is an inventor on patents licensed to companies developing microneedle-based products. This potential conflict of interest has been disclosed and is being managed by the Georgia Institute of Technology and Emory University.

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Correspondence to Mark R. Prausnitz.

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Andrews, S.N., Jeong, E. & Prausnitz, M.R. Transdermal Delivery of Molecules is Limited by Full Epidermis, Not Just Stratum Corneum. Pharm Res 30, 1099–1109 (2013).

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  • insulin
  • microdermabrasion
  • skin
  • stratum corneum
  • transdermal drug delivery
  • viable epidermis