The effect of two azones on the lateral lipid organization of human stratum corneum and its permeability

被引:21
作者
Pilgram G.S.K. [1 ]
Engelsma-van Pelt A.M. [1 ]
Koerten H.K. [1 ]
Bouwstra J.A. [2 ]
机构
[1] Center for Electron Microscopy, Leiden University Medical Center, Leiden, 2300 RA
[2] Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, 2300 RA
关键词
Barrier function; Cryo-electron microscopy; Electron diffraction; Enhancer; Penetration; Skin;
D O I
10.1023/A:1007547906856
中图分类号
学科分类号
摘要
Purpose. 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. Methods. 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. Results. 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. Conclusions. 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.
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页码:796 / 802
页数:6
相关论文
共 32 条
[1]
Shaw J., Chandrasekaran S., Controlled topical delivery of drugs for systemic action, Drug Metab. Rev., 8, pp. 223-233, (1978)
[2]
Pellett M.A., Roberts M.S., Hadgraft J., Supersaturated solutions evaluated with an in vitro stratum corneum tape stripping technique, Int. J. Pharm., 151, pp. 91-98, (1997)
[3]
Cornwell P.A., Barry B.W., Bouwstra J.A., Gooris G.S., Modes of action of terpene penetration enhancers in human skin
[4]
differential scanning calorimetry, small-angle X-ray diffraction and enhancer uptake studies, Int. J. Pharm., 127, pp. 9-26, (1996)
[5]
Tanojo H., Bos-Van Geest A., Bouwstra J.A., Junginger H.E., Bodde H.E., In vitro human skin barrier perturbation by oleic acid: Thermal analysis and freeze fracture electron microscopy studies, Thermochim. Acta, 293, pp. 77-85, (1997)
[6]
Hadgraft J., Peck J., Williams D.G., Pugh W.J., Allan G., Mechanisms of action of skin penetration enhancers/retarders: Azone and analogues, Int. J. Pharm., 141, pp. 17-25, (1996)
[7]
Van den Bergh B.A.I., Salomons-De Vries I., Bouwstra J.A., Interactions between liposomes and human stratum corneum studied by freeze-substitution electron microscopy, Int. J. Pharm., 167, pp. 57-67, (1998)
[8]
Pechtold L.A.R.M., Abraham W., Potts R.O., The influence of an electric field on ion and water accessibility to stratum corneum lipid lamellae, Pharm. Res., 13, pp. 1168-1173, (1996)
[9]
Kalia Y.N., Guy R.H., Interaction between penetration enhancers and iontophoresis: Effect on human skin impedance in vivo, J. Contr. Rel., 44, pp. 33-42, (1997)
[10]
Bouwstra J.A., Gooris G.S., Brussee J., Salomons-De Vries M.A., Bras W., The influence of alkyl-azones on the ordering of the lamellae in human stratum corneum, Int. J. Pharm., 79, pp. 141-148, (1992)