Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei 110, Taiwan.
J Control Release. 2011 Aug 10;153(3):240-8. doi: 10.1016/j.jconrel.2011.03.015. Epub 2011 Mar 22.
The aim of this study was to evaluate the ability of a low-fluence fractional erbium:yttrim-aluminum-garnet (Er:YAG) laser, with a wavelength of 2940 nm, for enhancing and controlling the skin permeation of imiquimod and macromolecules such as polypeptides and fluorescein isothiocyanate (FITC)-labeled dextran (FD). The in vitro permeation has been determined using a Franz diffusion cell, with porcine skin and nude mouse skin as the barriers. Hyperproliferative and ultraviolet (UV)-irradiated skins were also used as barrier models to mimic the clinical therapeutic conditions. Confocal laser scanning microscopy (CLSM) was used to examine the in vivo nude mouse skin uptake of peptide, FITC, and FD. Both in vitro and in vivo results indicated an improvement in permeant skin delivery by the laser. The laser fluence and number of passes were found to play important roles in controlling drug transport. Increases of 46- and 127-fold in imiquimod flux were detected using the respective fluences of 2 and 3 J/cm(2) with 4 pulses. An imiquimod concentration of 0.4% from aqueous vehicle with laser treatment was sufficient to approximate the flux from the commercial cream with an imiquimod dose of 5% without laser treatment, indicating a reduction of the drug dose by 125-fold. The enhancement of peptide permeation was size and sequence dependent, with the smaller molecular weight (MW) and more-hydrophilic entities showing greater enhancing effect. Skin permeation of FD with an MW of at least 150 kDa could be achieved with fractional laser irradiation. CLSM images revealed intense green fluorescence from the permeants after exposure of the skin to the laser. The follicular pathway was significant in laser-assisted permeation.
本研究旨在评估低能量 2940nm 铒：钇铝石榴石（Er:YAG）激光增强和控制咪喹莫特和大分子（如多肽和异硫氰酸荧光素（FITC）标记的葡聚糖（FD））经皮渗透的能力。使用Franz 扩散池，以猪皮和裸鼠皮作为屏障，测定体外渗透情况。还使用过度增生和紫外线（UV）辐照皮肤作为屏障模型，模拟临床治疗条件。共聚焦激光扫描显微镜（CLSM）用于检查肽、FITC 和 FD 在体内裸鼠皮肤中的摄取情况。体内和体外结果均表明激光可改善渗透物的皮肤传递。激光能量密度和脉冲数被发现对控制药物传输起着重要作用。分别使用 2 和 3 J/cm2 的能量密度和 4 个脉冲，咪喹莫特的通量增加了 46 倍和 127 倍。用激光处理的含 0.4%咪喹莫特的水相制剂的浓度足以接近无激光处理的含 5%咪喹莫特的商业乳膏的通量，表明药物剂量减少了 125 倍。肽渗透增强与分子大小和序列有关，分子量（MW）较小和更亲水的物质显示出更大的增强效果。经皮应用 Fractional 激光后，MW 至少为 150kDa 的 FD 可实现经皮渗透。CLSM 图像显示皮肤暴露于激光后，透皮剂显示出强烈的绿色荧光。毛囊途径在激光辅助渗透中起重要作用。
