| Summary: | 碩士 === 長庚大學 === 中醫學系天然藥物 === 100 === The resurfacing laser can ablate the skin to a determined depth, resulting in the increased absorption of the drugs or cosmetics. This study divided into two parts. The first project was to assess erbium:yttrium-aluminum-garnet (Er:YAG) laser resurfacing can increase skin permeability and the risk of excessive absorption of tetracycline and sunscreens. Ablation depths varied from reaching the stratum corneum (10 μm, 2.5 J/cm2) to approaching the epidermis (25 μm, 6.3 J/cm2) and upper dermis (40 μm, 10 J/cm2). Physiologic, histopathologic examinations and proteomic analysis could find that the laser was sufficient to disrupt the skin barrier and allowed the transport of the permeants into and across skin. A 25-μm ablation could increase tetracycline flux by 84 folds. A lesser enhancement (3 folds) was detected for tetracycline accumulation within skin. The laser had produced enhancement on oxybenzone skin deposition from 3~6-fold relative to the untreated group. No penetration across skin was shown regardless of titanium dioxide applied onto intact and laser-treated skin. However, the laser resurfacing increased skin deposition of titanium dioxide. The tetracycline absorption could be recovered to the level of intact skin by 3 days. More time was required for oxybenzone absorption. The second project aimed to evaluate the skin permeation enhancement mediated by fractional laser for different permeants, including small molecule drugs, macromolecules, and nanoparticles. The fractional CO2 laser using fluence of 2 or 4 mJ with spot densities of 100~400 spots/cm2. The laser could enhance the flux of small molecule drugs by a 2~5-fold as compared to intact skin and promote the flux of FD-20 and FD-40 from zero to 0.72 and 0.43 nmol/cm2/h. Fluorescence and confocal microscopic images demonstrated a significant increase in fluorescence accumulation and penetration depth of macromolecules and nanoparticles after laser exposure. The predominant routes for laser-assisted delivery was follicular transport. Skin barrier function determined by transepidermal water loss was completed by 12 h after irradiation, which was much faster than the conventional laser (4 days). The experimental results indicate that the dosing for postoperative treatment should be cautious and this work first elucidated the role of follicles on drug delivery enhanced by fractional laser.
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