Enhancement of percutaneous absorption by laurocapram.
The in vitro treatment of shed snake skin and hairless rat skin with laurocapram resulted in dramatic decreases in the amounts of cholesterol, phospholipids, and ceramides but not triglycerides in the skins. Scanning electron microscopic observations of hairless rat skin treated with laurocapram indicated looseness and cell separation of the stratum corneum probably caused by the extensive extraction of the intercellular lipids. An ESR study demonstrated the increased fluidity of the corneum lipids after laurocapram treatment. The apparent rotational correlation time of 16-doxyl-stearic acid was decreased by 1.6-2 times after treatment with laurocapram. No penetration of laurocapram itself through shed snake skin and hairless rat skin was detected in vitro, except when the reservoir solvent was 60% ethanol or propylene glycol. The enhancer was hardly metabolized during a 48-h incubation with skin homogenate. Pretreatment of shed snake skin with laurocapram increased significantly the penetration of sulfanilamide and indomethacin through the skin. These results indicate that laurocapram penetrating into the stratum corneum interacts with structured lipids in the intercellular channels and releases them, thereby enhancing the penetration of hydrophilic drugs through the channels. Additionally, laurocapram penetrating into the intracellular matrix of the corneum fluidizes the intracellular lipids and causes the reduction of diffusional resistance.
Ogiso
T
T
Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
Iwaki
M
M
Bechako
K
K
Tsutsumi
Y
Y
D000279:Administration, Cutaneous; D000818:Animals; D001381:Azepines / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D001692:Biological Transport; D004578:Electron Spin Resonance Spectroscopy; D004817:Epidermis / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000493:pharmacokinetics; D007424:Intracellular Fluid / Q000378:metabolism; D008055:Lipids / Q000032:analysis / Q000502:physiology; D008297:Male; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D051381:Rats; D012867:Skin / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D012911:Snakes; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000493:pharmacokinetics
D001381:Azepines; D008055:Lipids; D013424:Sulfanilamides; C035229:laurocapram; D000077145:Sulfanilamide; D007213:Indomethacin