The mode of promoting activity of O-ethylmenthol as a transdermal absorption enhancer.
OBJECTIVE
The mode of action of O-ethylmenthol (MET), a promising compound to enhance transdermal drug delivery, was elucidated. Morphology of the skin treated with MET was investigated employing a laser scanning confocal microscopy.


METHODS
Confocal scanning laser microscope and laser scanning microscope were employed for the morphological evaluation of the stratum corneum. To evaluate the fluidity of intercellular lipids by treatment with MET, liposomes composed of the stratum corneum lipids were prepared.


RESULTS
Distribution amounts of the fluorescent probes greatly increased in the intercellular regions of the stratum corneum treated with 40% ethanol containing MET. Based on the skin surface observations, the difference in relative height between keratinocytes and intercellular regions was defined as DeltaH = DeltaH(keratinocytes) - DeltaH(intercellular space), where DeltaH is the difference in relative height, DeltaH(keratinocytes) is the height of center region in the keratinocytes, and DeltaH(intercellular space) is the height of the intercellular space. DeltaH values became negative in the skin surface treated with 40% ethanol containing MET because of the swelling in the intercellular regions. DeltaH values changed from positive to negative 15-30 min after the administration of MET. A very short period of application of MET was sufficient to induce its promoting activity.


CONCLUSIONS
MET was able to change the structure of the intercellular lipids, thereby enhancing both the partitioning and diffusion of drugs through the skin.
Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan. obata@hoshi.ac.jp
Yasuko
Y
Obata
Yoshimichi
Y
Maruyama
Kozo
K
Takayama
D000279:Administration, Cutaneous; D000465:Algorithms; D000818:Animals; D016880:Anisotropy; D004337:Drug Carriers; D005079:Excipients / Q000494:pharmacology*; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000378:metabolism / Q000648:ultrastructure; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008610:Menthol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008812:Mice, Hairless; D018613:Microscopy, Confocal; D019999:Pharmaceutical Solutions; D012869:Skin Absorption / Q000187:drug effects*
D004337:Drug Carriers; D005079:Excipients; D008055:Lipids; D008081:Liposomes; C401982:O-ethylmenthol; D019999:Pharmaceutical Solutions; D008610:Menthol