Kinetic study of cutaneous and subcutaneous distribution following topical application of [7,8- 14C]rac-α-lipoic acid onto hairless mice

To diminish oxidative injury, topically applied antioxidants must reach susceptible cells. α-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-α-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]-α-lipoic acid were determined in strippings and slices of epidermis (4 × 5 μm), dermis, and subcutaneous fat (10 × 10 μm, 20 × 20 μm). The rate of [ 14C]-α-lipoic acid absorption into skin was constant by 30 min (0.10 ± 0.01 nmol/cm 2/min); maximum skin concentrations were reached by 2 hr. The [ 14C]-α-lipoic acid penetration kinetics into the first layer of the stratum corneum predicted its penetration through the stratum corneum and subsequent percutaneous absorp- tion ( r 2 = 0.96, P < 0.02). Cutaneous absorption of unlabeled α-lipoic acid and its reduction to the more potent antioxidant form, dihydrolipoic acid, were also demonstrated, using HPLC analysis with electrochemical detection. In conclusion, α-lipoic acid topically applied to skin penetrated readily, and was reduced to dihydrolipoic acid. Thus, α-lipoic acid could potentiate skin antioxidant protection.