A lamellar matrix model for stratum corneum intercellular lipids .2. Effect of geometry of the stratum corneum on permeation of model drugs 5-fluorouracil and oestradiol
A lamellar matrix model for stratum corneum intercellular lipids .2. Effect of geometry of the stratum corneum on permeation of model drugs 5-fluorouracil and oestradiol
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DOI：
10.1016/0378-5173(95)04307-1
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发表时间：
1996-04-19
影响因子：
5.8
通讯作者：
Barry, BW
中科院分区：
文献类型：
--
作者：
Moghimi, HR;Williams, AC;Barry, BW
大多数药物透皮给药的主要屏障是角质层（SC）的层状细胞间脂质结构域。与其他脂质屏障相比，SC的低渗透性部分是由于其几何形状。在这里，使用SC细胞间脂质的层状模型基质研究了SC的几何形状对5-氟尿嘧啶（5-FU）-模型亲水性药物-和雌二醇（OE）-模型亲脂性药物-渗透的影响。在32 ℃下的释放研究表明，5-FU和OE在基质中的扩散系数分别约为人表皮表观值的6000-7000倍和60-260倍，与理论考虑一致。13 - 44 ℃的释放研究表明，5-FU在基质的主要转变温度（35 ℃）附近具有最大扩散系数，与文献中报告的其他层状系统一致。5-FU在基质中的扩散活化能为27.8 kcal，mol（-1），与人表皮数据相关性良好。然后将释放实验与渗透研究相结合，并从基质数据预测模型药物在32 ℃下通过SC的渗透性。5-FU（5.5-18 x 10（-5）cm h（-1））和OE（0.07-0.24 x 10（-3）cm h（-1））的预测渗透系数与人体表皮数据一致。我们的研究结果表明SC形态对药物的经皮吸收的影响，并说明5-FU和OE通过细胞间脂质渗透SC。
The principal barrier to transdermal delivery of most drugs is the lamellar intercellular lipid domain of the stratum corneum (SC). The low permeability of SC in comparison to other lipid barriers is in part due to its geometry. Here, effect of geometry of the SC on permeation of 5-fluorouracil (5-FU) - a model hydrophilic drug - and oestradiol (OE) - a model lipophilic drug - was investigated using a lamellar model matrix for SC intercellular lipids. Release studies at 32 degrees C showed that the diffusion coefficients of 5-FU and OE in the matrix are approximately 6000-7000- and 60-260-times greater, respectively, than apparent human epidermis values, in good agreement with theoretical considerations. Release studies from 13 to 44 degrees C revealed that 5-FU has a maximum diffusion coefficient around the main transition temperature of the matrix (35 degrees C) in agreement with other lamellar systems reported in the literature. The diffusional activation energy of 5-FU in the matrix was 27.8 kcal, mol(-1) which correlates well with human epidermal data. Release experiments were then combined with permeation studies and the permeability of model drugs through the SC at 32 degrees C was predicted from matrix data. The predicted permeability coefficients of 5-FU (5.5-18 x 10(-5) cm h(-1)) and OE (0.07-0.24 x 10(-3) cm h(-1)) were in agreement with human epidermis data. Our results show the effect of the SC morphology on the percutaneous absorption of drugs and illustrate that 5-FU and OE permeate the SC through intercellular lipids.