title: Microsecond thermal ablation of skin for transdermal drug delivery.
abstract: Thermal ablation is a promising mechanism to increase permeability of the skin's outer barrier layer of stratum corneum while sparing deeper living tissues. In this study, finite element modeling predicted that the skin surface should only be heated on the microsecond timescale in order to avoid significant temperature rises in living cells and nerve endings in deeper tissue. To achieve such short thermal pulses, we developed a microdevice that rapidly heats a few microliters of water by an electrical discharge and ejects the resulting superheated steam at the skin surface on a timescale on the order of 100 μs. According to its design, we showed that this microdevice selectively removed stratum corneum of cadaver skin without significantly removing deeper tissue. This one-dimensional depth control was supplemented through the use of a masking film containing 100 μm-diameter holes placed on the skin surface during ablation to define the ablated skin area and thereby provide three-dimensional control over tissue removal. Using this approach, thermal ablation increased skin permeability to sulforhodamine B and bovine serum albumin by at least 1000-fold in vitro. We conclude that microsecond thermal ablation of skin can selectively remove stratum corneum and thereby dramatically increase skin permeability for transdermal drug delivery.
authors: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors: Jeong Woo
authors: JW
authors: Lee
authors: Priya
authors: P
authors: Gadiraju
authors: Jung-Hwan
authors: JH
authors: Park
authors: Mark G
authors: MG
authors: Allen
authors: Mark R
authors: MR
authors: Prausnitz
references: J Control Release. 2010 Aug 17;146(1):31-6
references: 20678988
references: Nat Biotechnol. 2008 Nov;26(11):1261-8
references: 18997767
references: Pharm Res. 2007 Jul;24(7):1389-95
references: 17443396
references: Int J Pharm. 2008 Dec 8;364(2):227-36
references: 18805472
references: Adv Drug Deliv Rev. 2004 Mar 27;56(5):603-18
references: 15019749
references: Pharm Res. 2005 Apr;22(4):550-5
references: 15846462
references: Int J Pharm. 2008 Jul 9;359(1-2):94-103
references: 18455889
references: J Invest Dermatol. 1977 Sep;69(3):333-8
references: 894075
references: Adv Drug Deliv Rev. 2008 Jun 30;60(10):1218-23
references: 18450318
references: Annu Rev Biomed Eng. 2000;2:477-509
references: 11701521
references: Curr Top Microbiol Immunol. 2009;333:369-93
references: 19768415
references: J Control Release. 2003 Apr 29;89(2):311-20
references: 12711453
references: Adv Skin Wound Care. 2004 Oct;17(8):417-25
references: 15492677
references: Brain. 2002 Mar;125(Pt 3):501-10
references: 11872608
references: Int J Pharm. 2006 Jul 6;317(1):1-6
references: 16713690
references: Lasers Surg Med. 2002;31(4):252-6
references: 12355570
references: Gene Ther. 2003 Feb;10(3):251-60
references: 12571633