title: Femtosecond pulsed laser ablation to enhance drug delivery across the skin.
abstract: Laser poration of the skin locally removes its outermost, barrier layer, and thereby provides a route for the diffusion of topically applied drugs. Ideally, no thermal damage would surround the pores created in the skin, as tissue coagulation would be expected to limit drug diffusion. Here, a femtosecond pulsed fiber laser is used to porate mammalian skin ex vivo. This first application of a hollow core negative curvature fiber (HC-NCF) to convey a femtosecond pulsed, visible laser beam results in reproducible skin poration. The effect of applying ink to the skin surface, prior to ultra-short pulsed ablation, has been examined and Raman spectroscopy reveals that the least, collateral thermal damage occurs in inked skin. Pre-application of ink reduces the laser power threshold for poration, an effect attributed to the initiation of plasma formation by thermionic electron emission from the dye in the ink. Poration under these conditions significantly increases the percutaneous permeation of caffeine in vitro. Dye-enhanced, plasma-mediated ablation of the skin is therefore a potentially advantageous approach to enhance topical/transdermal drug absorption. The combination of a fiber laser and a HC-NCF, capable of emitting and delivering femtosecond pulsed, visible light, may permit a compact poration device to be developed.
authors.affiliation: Department of Physics, University of Bath, Bath, BA2 7AY, UK.|Department of Pharmacy & Pharmacology, University of Bath, Bath, BA2 7AY, UK.
authors.forename: Hazel
authors.initials: H
authors.lastname: Garvie-Cook
authors.affiliation: Department of Physics, University of Bath, Bath, BA2 7AY, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Stone
authors.affiliation: Department of Physics, University of Bath, Bath, BA2 7AY, UK.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Pharmacy & Pharmacology, University of Bath, Bath, BA2 7AY, UK.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Guy
authors.affiliation: Department of Physics, University of Bath, Bath, BA2 7AY, UK. s.gordeev@bath.ac.uk.
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Gordeev
mesh_terms: D055011:Ablation Techniques; D000818:Animals; D002110:Caffeine / Q000378:metabolism; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D007834:Lasers; D055100:Optical Fibers; D016062:Porosity; D012867:Skin / Q000378:metabolism*; D013552:Swine; D013997:Time Factors
chemical_list: D002110:Caffeine
keywords: Raman spectroscopy; fiber laser; optical fibers; pulsed laser tissue ablation; skin drug administration