Purpose: 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 CO2 laser, using fluence of 2 or 4 mJ with densities of 100 ∼ 400 spots/cm2. 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/cm2 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. CO2 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.
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