Division of Physical Chemistry, The Center for Chemistry and Chemical Engineering, Lund University, Lund, Sweden.
Biophys J. 2013 Jun 18;104(12):2639-50. doi: 10.1016/j.bpj.2013.05.008.
The stratum corneum (SC) is an effective permeability barrier. One strategy to increase drug delivery across skin is to increase the hydration. A detailed description of how hydration affects skin permeability requires characterization of both macroscopic and molecular properties and how they respond to hydration. We explore this issue by performing impedance experiments on excised skin membranes in the frequency range 1 Hz to 0.2 MHz under the influence of a varying gradient in water activity (aw). Hydration/dehydration induces reversible changes of membrane resistance and effective capacitance. On average, the membrane resistance is 14 times lower and the effective capacitance is 1.5 times higher when the outermost SC membrane is exposed to hydrating conditions (aw = 0.992), as compared to the case of more dehydrating conditions (aw = 0.826). Molecular insight into the hydration effects on the SC components is provided by natural-abundance (13)C polarization transfer solid-state NMR and x-ray diffraction under similar hydration conditions. Hydration has a significant effect on the dynamics of the keratin filament terminals and increases the interchain spacing of the filaments. The SC lipids are organized into lamellar structures with ∼ 12.6 nm spacing and hexagonal hydrocarbon chain packing with mainly all-trans configuration of the acyl chains, irrespective of hydration state. Subtle changes in the dynamics of the lipids due to mobilization and incorporation of cholesterol and long-chain lipid species into the fluid lipid fraction is suggested to occur upon hydration, which can explain the changes of the impedance response. The results presented here provide information that is useful in explaining the effect of hydration on skin permeability.
角质层（SC）是一种有效的渗透屏障。增加药物经皮传递的一种策略是增加皮肤的水合作用。详细描述水合作用如何影响皮肤渗透性需要对宏观和分子性质及其对水合作用的响应进行特征描述。我们通过在水活度（aw）变化梯度的影响下，在 1 Hz 至 0.2 MHz 的频率范围内对离体皮肤膜进行阻抗实验来研究这个问题。水合/脱水会引起膜电阻和有效电容的可逆变化。平均而言，当最外层 SC 膜暴露于水合条件（aw = 0.992）时，膜电阻低 14 倍，有效电容高 1.5 倍，与更脱水条件（aw = 0.826）相比。在类似水合条件下，通过天然丰度（13）C 极化转移固态 NMR 和 X 射线衍射，提供了水合作用对 SC 成分影响的分子见解。水合作用对角蛋白丝末端的动力学有显著影响，并增加了丝之间的间隔。SC 脂质组织成具有约 12.6 nm 间隔的层状结构和具有主要全反式构象的六边形烃链堆积，与水合状态无关。由于胆固醇和长链脂质种类向流体脂质部分的迁移和掺入，脂质的动力学发生微妙变化，这可以解释阻抗响应的变化。这里呈现的结果提供了对水合作用对皮肤渗透性影响的解释有用的信息。
