Graduate Institute of Medical Sciences,, Taipei Medical University, Taipei, 110, Taiwan.
Pharm Res. 2013 Mar;30(3):792-802. doi: 10.1007/s11095-012-0920-4. Epub 2012 Nov 10.
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.
评估不同透皮促进剂（包括对苯二酚、咪喹莫特、异硫氰酸荧光素标记葡聚糖（FD）和量子点）经飞点激光介导后的经皮渗透增强作用。
采用密度为 100 ～ 400 个光斑/cm2 的 2 或 4 mJ 激光单次辐照皮肤。进行体外和体内皮肤渗透实验。使用荧光和共聚焦显微镜进行示踪给药途径。
与完整皮肤相比，激光使小分子药物的通量增加了 2 ～ 5 倍。400 个光斑/cm2 密度、4 mJ 的激光促进 20 和 40 kDa FD 的通量分别从 0（被动传输）增加到 0.72 和 0.43 nmol/cm2/h。显微镜图像显示，激光暴露后大分子和纳米颗粒的荧光积累和渗透深度显著增加。激光辅助递药的主要途径可能是细胞间和毛囊传输。CO2 激光辐照使咪喹莫特在毛囊中的沉积增加了 13 倍。激光介导的毛囊传输可以将渗透物递送至更深的层次。经表皮水分丢失（TEWL）测定的皮肤屏障功能在照射后 12 小时内完全恢复，比传统激光治疗（4 天）快得多。
飞点激光可以选择性地增强透皮促进剂（如咪喹莫特和 FD）向毛囊的靶向递送，但不能增强对苯二酚的递送，这表明选择可行的药物进行激光辅助毛囊递药非常重要。
