In vivo and in vitro percutaneous absorption of cancer preventive flavonoid apigenin in different vehicles in mouse skin.

PURPOSE: In vivo and in vitro percutaneous absorption of apigenin was investigated in three vehicles previously used in cancer prevention studies to determine the drug delivery properties for optimal chemo-preventive activity.

METHODS

In vivo percutaneous absorption of apigenin on SENCAR mice was studied with DMSO and acetone/DMSO (A/D, 4:1) vehicle. In vitro percutaneous absorption studies used whole mouse skin, without subcutaneous fat, mounted on Franz diffusion cells with 37 degrees C Dulbecco's phosphate-buffered saline as the receptor fluid. The skin was treated with [G-3H]-apigenin in DMSO, A/D (4:1), or propylene glycol/DMSO (PG/D, 4:1).

RESULTS

Apigenin uptake by epidermal cells and distribution in epidermis following in vivo topical treatment in two vehicles was in the order of A/D > DMSO, while apigenin distribution in dermis and subcutaneous fat was not different between DMSO and A/D. Total apigenin absorption in mouse skin in vitro was in the order of A/D > DMSO > PG/D. However, apigenin sub-tissue distribution within epidermis determined by tape-stripping and by determination of apigenin in dermal and epidermal tissue indicated that DMSO delivered more apigenin into viable epidermis than A/D while A/D deposited more apigenin in the stratum corneum. Apigenin absorption in mouse skin with DMSO or A/D showed saturation kinetics while apigenin in PG/D showed very low absorption initially and non-saturated absorption in a period of 6 hr. HPLC-scintillation profiles of in vitro samples showed no evidence of apigenin metabolism in mouse skin.

CONCLUSIONS

Delivering apigenin into viable epidermis appears to be a necessary property for an apigenin formulation to be effective in skin cancer prevention.