title: Skin permeation of small-molecule drugs, macromolecules, and nanoparticles mediated by a fractional carbon dioxide laser: the role of hair follicles.
abstract: OBJECTIVE
  To evaluate skin permeation enhancement mediated by fractional laser for different permeants, including hydroquinone, imiquimod, fluorescein isothiocyanate-labeled dextran (FD), and quantum dots.
  
  
  METHODS
  Skin received a single irradiation of a fractional CO(2) laser, using fluence of 2 or 4 mJ with densities of 100 ∼ 400 spots/cm(2). In vitro and in vivo skin penetration experiments were performed. Fluorescence and confocal microscopies for imaging delivery pathways were used.
  
  
  RESULTS
  The laser enhanced flux of small-molecule drugs 2 ∼ 5-fold compared to intact skin. A laser fluence of 4 mJ with a 400-spot/cm(2) density promoted FD flux at 20 and 40 kDa from 0 (passive transport) to 0.72 and 0.43 nmol/cm(2)/h, respectively. Microscopic images demonstrated a significant increase in fluorescence accumulation and penetration depth of macromolecules and nanoparticles after laser exposure. Predominant routes for laser-assisted delivery may be intercellular and follicular transport. CO(2) laser irradiation produced 13-fold enhancement in follicular deposition of imiquimod. Laser-mediated follicular transport could deliver permeants to deeper strata. Skin barrier function as determined by transepidermal water loss completely recovered by 12 h after irradiation, much faster than conventional laser treatment (4 days).
  
  
  CONCLUSIONS
  Fractional laser could selectively enhance permeant targeting to follicles such as imiquimod and FD but not hydroquinone, indicating the importance of selecting feasible drugs for laser-assisted follicle delivery.
authors.affiliation: Graduate Institute of Medical Sciences,, Taipei Medical University, Taipei, 110, Taiwan.
authors.forename: Woan-Ruoh
authors.initials: WR
authors.lastname: Lee
authors.forename: Shing-Chuan
authors.initials: SC
authors.lastname: Shen
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Al-Suwayeh
authors.forename: Hung-Hsu
authors.initials: HH
authors.lastname: Yang
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Li
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005260:Female; D018859:Hair Follicle / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D054020:Lasers, Gas; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000032:analysis*; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D012869:Skin Absorption / Q000528:radiation effects*; D054852:Small Molecule Libraries / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D054852:Small Molecule Libraries