Kinetic study of cutaneous and subcutaneous distribution following topical application of [7,8-14C]rac-alpha-lipoic acid onto hairless mice.
To diminish oxidative injury, topically applied antioxidants must reach susceptible cells. alpha-Lipoic acid is a potent thiol antioxidant that might be useful for skin protection; therefore, its skin penetration kinetics were assessed. The cutaneous and subcutaneous distributions of [7,8-14C]rac-alpha-lipoic acid were studied in anesthetized hairless mice after application of a 5% solution in propylene glycol for 0.5 to 4 hr. The mice were killed; then the skin was washed, and the stratum corneum was removed by 10 cellophane tape strippings. A punch biopsy of the frozen, stripped skin was sectioned, and amounts of [14C]-alpha-lipoic acid were determined in strippings and slices of epidermis (4 x 5 microns), dermis, and subcutaneous fat (10 x 10 microns, 20 x 20 microns). The rate of [14C]-alpha-lipoic acid absorption into skin was constant by 30 min (0.10 +/- 0.01 nmol/cm2/min); maximum skin concentrations were reached by 2 hr. The [14C]-alpha-lipoic acid penetration kinetics into the first layer of the stratum corneum predicted its penetration through the stratum corneum and subsequent percutaneous absorption (r2 = 0.96, P < 0.02). Cutaneous absorption of unlabeled alpha-lipoic acid and its reduction to the more potent antioxidant form, dihydrolipoic acid, were also demonstrated, using HPLC analysis with electrochemical detection. In conclusion, alpha-lipoic acid topically applied to skin penetrated readily, and was reduced to dihydrolipoic acid. Thus, alpha-lipoic acid could potentiate skin antioxidant protection.
Podda
M
M
University of California Berkeley, Department of Molecular and Cell Biology 94720-3200, USA.
Rallis
M
M
Traber
M G
MG
Packer
L
L
Maibach
H I
HI
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D008815:Mice, Inbred Strains; D012867:Skin / Q000187:drug effects*; D008063:Thioctic Acid / Q000493:pharmacokinetics*
D008063:Thioctic Acid