Skin Permeation of Small-Molecule Drugs, Macromolecules, and Nanoparticles Mediated by a Fractional Carbon Dioxide Laser: The Role of Hair Follicles

To evaluate skin permeation enhancement mediated by fractional laser for different permeants, including hydroquinone, imiquimod, fluorescein isothiocyanate-labeled dextran (FD), and quantum dots.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.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).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.