Pilgram G S, Engelsma-van Pelt A M, Koerten H K, Bouwstra J A
Center for Electron Microscopy, Leiden University Medical Center, The Netherlands.
Pharm Res. 2000 Jul;17(7):796-802. doi: 10.1023/a:1007547906856.
Investigation of the relationship between changes in human SC lipid organization induced by N-alkyl-azocycloheptane-2-one and SC permeability to the model compound HgCl2.
Human dermatomed skin was treated with propylene glycol (PG), oleyl-Azone (OAz) or dodecyl-Azone (DAz) in 0.15 M PG. Untreated skin served as control. The lateral lipid organization was studied by electron diffraction. Hg was measured on tape-strips by X-ray microanalysis and in the acceptor phase by atom absorption spectrometry.
In control and PG treated samples, the lipid packing was mainly orthorhombic, while a small fraction was hexagonal. In OAz and DAz treated samples, the orthorhombic lipid organization remained, however, the hexagonal packing was recorded less frequently. The amount of Hg decreased as a function of depth in all SC samples, however, the penetration profile increased significantly upon OAz treatment. The cumulative amount of Hg in the acceptor phase of OAz treated samples also increased significantly compared to control and PG treated samples.
The increased penetration of Hg into OAz treated skin could not be related to an orthorhombic-hexagonal phase transition. Alternatively, phase separation of OAz and/or formation of grain boundaries might affect SC permeability, hereby increasing Hg penetration. A similar mechanism is proposed for DAz.
研究N-烷基-氮杂环庚烷-2-酮诱导的人皮肤角质层（SC）脂质组织变化与SC对模型化合物HgCl₂的渗透性之间的关系。
将人离体皮肤用0.15 M丙二醇（PG）中的丙二醇、油醇-氮酮（OAz）或十二烷基-氮酮（DAz）处理。未处理的皮肤作为对照。通过电子衍射研究横向脂质组织。通过X射线微分析在胶带条上测量Hg，并通过原子吸收光谱法在接受相中测量Hg。
在对照和PG处理的样品中，脂质堆积主要为正交晶系，而一小部分为六方晶系。在OAz和DAz处理的样品中，正交晶系脂质组织仍然存在，然而，六方堆积的记录频率较低。在所有SC样品中，Hg的量随深度而减少，然而，经OAz处理后渗透曲线显著增加。与对照和PG处理的样品相比，OAz处理样品的接受相中Hg的累积量也显著增加。
Hg进入OAz处理皮肤的渗透率增加与正交晶系-六方晶系相变无关。另外，OAz的相分离和/或晶界的形成可能会影响SC的渗透性，从而增加Hg的渗透。对DAz也提出了类似的机制。
