Mechanism of skin penetration-enhancing effect by laurocapram.
In order to clarify the mechanism of action of laurocapram (Azone) on the skin permeation of drugs, the following experiments were done. First, the effect of Azone on the skin components was compared with that of other penetration enhancers. Azone markedly fluidized liposomal lipids (as a model lipid system) compared with other enhancers. Ethanol extracted large amounts of the stratum corneum lipids, whereas Azone did not. These results suggest that the effect of Azone on the lipids in the stratum corneum is not the same as that of ethanol. In addition, ethanol increased the amount of free sulfhydryl (SH) group of keratin in the stratum corneum, whereas Azone did not directly affect the stratum corneum protein. Azone increased water content in the stratum corneum, as measured by skin conductance. This effect might be a reason for the action of Azone. For further understanding, the enhancing effects of Azone on the skin permeation of several model compounds (alcohols, sugars, and inorganic ions) were compared with the effects of pretreatment with distilled water, which was thought to increase water-holding capacity, and pretreatment with ethanol, which was thought to affect the lipids and protein in the skin barrier (i.e., stratum corneum). Pretreatment with water or ethanol enhanced skin permeation of hydrophilic compounds, whereas they decreased that of octanol, a hydrophobic compound. The tendency of Azone to increase or decrease the skin permeation rate of most compounds was similar to that of pretreatment with water or ethanol. However, the effect of Azone on the skin permeation of inorganic ions was relatively low, whereas that of pretreatment with water or ethanol was high.(ABSTRACT TRUNCATED AT 250 WORDS)
Sugibayashi
K
K
Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
Nakayama
S
S
Seki
T
T
Hosoya
K
K
Morimoto
Y
Y
D000438:Alcohols / Q000493:pharmacokinetics; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002241:Carbohydrates / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D007477:Ions; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000378:metabolism; D008297:Male; D051381:Rats; D012867:Skin / Q000737:chemistry / Q000187:drug effects*; D012869:Skin Absorption / Q000187:drug effects*
D000438:Alcohols; D001381:Azepines; D002241:Carbohydrates; D007477:Ions; D008055:Lipids; D008081:Liposomes; C035229:laurocapram; D000431:Ethanol