Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan; Department of Dermatology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan.
Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; Aesthetic Medical Center, Department of Dermatology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan.
Int J Pharm. 2019 Jun 10;564:48-58. doi: 10.1016/j.ijpharm.2019.04.043. Epub 2019 Apr 15.
Fractional CO laser treatment has been used in some clinical trials to promote topical drug delivery. Currently, there is no standard for laser settings to achieve a feasible therapy. The cutaneous recovery following laser treatment and its influence on drug absorption have not been well explored. This study evaluated the kinetics of laser-treated skin-barrier restoration and drug permeation in nude mice. The skin recovery and observation of the process were characterized by transdermal water loss (TEWL), erythema measurement, gross appearance, optical microscopy, and scanning electron microscopy (SEM). The skin absorption of a lipophilic small permeant (tretinoin), a hydrophilic small permeant (acyclovir), and a large molecule (fluorescein isothiocyanate dextran 4 kDa, FD4) was examined in vitro using Franz cell. TEWL suggested that the laser-treated skin restored its barrier function at 16 h after irradiation. The fractional laser produced microchannels of about 150 μm in diameter and 25 μm in depth that were surrounded with thermal coagulation. The bright-field imaging indicated that the micropores were progressively closed during the recovery period but had not completely closed even after a 16-h recovery. The laser treatment led to a rapid tretinoin penetration across the skin immediately after irradiation, with a 5-fold enhancement compared to intact skin. This enhancement was gradually reduced following the increase of recovery time. Conversely, the acyclovir and FD4 permeation peaked at 1-2 h post-irradiation. The FD4 flux was even elevated as the recovery time increased. The reasons for this could have been the subsequent inflammation after laser exposure and the deficient tight junction (TJ) barrier. The confocal imaging demonstrated the perpendicular diffusion of rhodamine B and FD4 through microchannels immediately after laser exposure. The lateral diffusion from the microchannels was observed at 2 h post-irradiation. Our results revealed a time-dependent recovery of skin permeation. The time frame for applying the drugs after laser irradiation was dependent upon the permeants and their various physicochemical properties.
分束 CO2 激光治疗已被应用于一些临床试验中，以促进局部药物递送。目前，尚无实现可行治疗的激光设置标准。激光治疗后皮肤屏障的恢复及其对药物吸收的影响尚未得到很好的探索。本研究评估了激光处理皮肤屏障恢复和药物渗透的动力学。通过经皮水分流失（TEWL）、红斑测量、肉眼观察、光学显微镜和扫描电子显微镜（SEM）对皮肤恢复和过程进行了特征描述。采用Franz 细胞体外研究了亲脂性小分子透皮剂（维甲酸）、亲水性小分子透皮剂（阿昔洛韦）和大分子（异硫氰酸荧光素右旋糖酐 4 kDa，FD4）的皮肤吸收。TEWL 表明，激光处理后的皮肤在照射后 16 小时恢复其屏障功能。分束激光产生了约 150 µm 直径和 25 µm 深度的微通道，周围有热凝固。明场成像表明，在恢复期间微孔逐渐关闭，但即使在 16 小时恢复后也未完全关闭。激光处理导致照射后立即迅速穿透皮肤的维甲酸，与完整皮肤相比增强了 5 倍。随着恢复时间的增加，这种增强逐渐降低。相反，阿昔洛韦和 FD4 的渗透在照射后 1-2 小时达到峰值。随着恢复时间的增加，FD4 的通量甚至升高。其原因可能是激光暴露后的后续炎症和紧密连接（TJ）屏障不足。共聚焦成像显示，照射后立即通过微通道垂直扩散罗丹明 B 和 FD4。在照射后 2 小时观察到从微通道的侧向扩散。我们的结果显示皮肤渗透具有时间依赖性恢复。在激光照射后应用药物的时间框架取决于渗透物及其各种物理化学性质。
