Pellanda C, Strub C, Figueiredo V, Rufli T, Imanidis G, Surber C
Hospital Pharmacy, University Hospital Basel, Basel, Switzerland.
Skin Pharmacol Physiol. 2007;20(1):50-6. doi: 10.1159/000096172. Epub 2006 Oct 11.
BACKGROUND/AIMS: Occlusion by covering the skin with an impermeable wrap enhances skin hydration, affects drug absorption and can induce the formation of a drug reservoir within the stratum corneum. This is desired in local therapy with topical corticosteroids. The aim of the study was to investigate the effect of occlusion before (experiment 1) and after (experiment 2) application on the penetration of triamcinolone acetonide (TACA) into the stratum corneum.
The experiments were conducted on the forearms of 10 healthy volunteers. In experiment 1, 100 microg/cm(2) TACA in acetone were applied on 3 sites per arm, one arm having been pre-occluded for 16 h. In experiment 2, the same dose was applied on 2 sites per arm, and one arm was occluded after application until skin sampling. Stratum corneum samples were removed by tape stripping at 0.5, 4 and 24 h (experiment 1) and 4 and 24 h (experiment 2) after application. Corneocytes and TACA were quantified by ultraviolet-visible spectroscopy and HPLC, respectively. The total TACA amount penetrated into the stratum corneum was evaluated by multifactor ANOVA.
TACA penetration into the stratum corneum with and without pre-occlusion (experiment 1) showed no significant difference and decreased with time. Occlusion after application (experiment 2) produced a marked TACA accumulation within the stratum corneum, which persisted for 24 h.
Pre-occlusion showed no effect on the topical bioavailability of TACA in the stratum corneum. In contrast, post-occlusion enhanced the TACA penetration by a factor of 2, favouring the development of a drug reservoir.
背景/目的：用不透性敷料覆盖皮肤造成的封闭可增强皮肤水合作用，影响药物吸收，并能在角质层内诱导形成药物储库。这在局部使用外用皮质类固醇治疗中是有益的。本研究的目的是调查在应用曲安奈德（TACA）之前（实验1）和之后（实验2）进行封闭对其渗透进入角质层的影响。
在10名健康志愿者的前臂上进行实验。在实验1中，每只手臂的3个部位涂抹含100μg/cm² TACA的丙酮溶液，其中一只手臂预先封闭16小时。在实验2中，每只手臂的2个部位涂抹相同剂量的药物，并且在涂抹后对一只手臂进行封闭直至取皮肤样本。在涂抹后0.5、4和24小时（实验1）以及4和24小时（实验2）通过胶带剥离法获取角质层样本。分别通过紫外可见光谱法和高效液相色谱法对角质形成细胞和TACA进行定量。通过多因素方差分析评估渗透进入角质层的TACA总量。
在有或没有预先封闭的情况下（实验1），TACA渗透进入角质层没有显著差异，且随时间下降。涂抹后封闭（实验2）导致TACA在角质层内显著蓄积，并持续24小时。
预先封闭对TACA在角质层中的局部生物利用度没有影响。相反，涂抹后封闭使TACA的渗透增加了2倍，有利于药物储库的形成。
