title: In vivo and in vitro percutaneous absorption of cancer preventive flavonoid apigenin in different vehicles in mouse skin.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha 68198, USA.
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.forename: D F
authors.initials: DF
authors.lastname: Birt
mesh_terms: D000096:Acetone / Q000494:pharmacology; D000279:Administration, Cutaneous; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D020843:Chamomile; D002851:Chromatography, High Pressure Liquid; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004817:Epidermis / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D018632:Mice, Inbred SENCAR; D009822:Oils, Volatile / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014677:Pharmaceutical Vehicles / Q000494:pharmacology*; D010946:Plants, Medicinal; D011409:Propylene Glycols / Q000494:pharmacology; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D014018:Tissue Distribution
chemical_list: D016588:Anticarcinogenic Agents; D005419:Flavonoids; D009822:Oils, Volatile; D014677:Pharmaceutical Vehicles; D011409:Propylene Glycols; D000096:Acetone; D004121:Dimethyl Sulfoxide