PENETRATION OF SPIN-LABELED DIHYDROLIPOATE INTO THE SKIN OF HAIRLESS MICE - MODIFICATION OF EPIDERMAL AND DERMAL POLARITY

Electron paramagnetic resonance (EPR) imaging with the modulated field gradient technique is a novel method to investigate skin biophysical and biochemical properties employing specific nitroxide spin probes. U sing this method, a distinct increase in polarity from epidermis towar ds lower dermis is observed with the spin label di-t-butylnitroxide (D TBN). With proxylmaleimide a considerable increase in mobility is foun d, when epidermis is compared with dermal compartments. The effect of the natural antioxidant dihydrolipoate on skin membrane polarity was s tudied. Skin penetration of spin labeled dihydrolipoate was investigat ed by EPR imaging. The results indicated that dihydrolipoate also incr eases membrane polarity. The biophysical and biochemical changes in th e epidermis and dermis as revealed by spatial imaging, provide indirec t evidence for skin penetration of dihydrolipoate. This conclusion was supported by the finding that spin labeled derivatives of dihydrolipo ate and lipoate were detected inside epidermis and dermis by EPR imagi ng. This study demonstrates the feasibility of EPR imaging to investig ate pharmacodynamic and pharmacokinetic properties of spin labeled dru gs in skin.