DIFFUSION OF ESTRADIOL FROM NONIONIC SURFACTANT VESICLES THROUGH HUMAN STRATUM-CORNEUM IN-VITRO

The effect of encapsulation of estradiol into non-ionic surfactant ves icles on the diffusion through human stratum corneum in vitro was inve stigated. Non-ionic surfactant vesicles were prepared from polyoxyethy lene alkyl ether surfactants (C(n)EO(m)) and sucrose ester surfactants (Wasag-7 and Wasag-15) with cholesterol, dicetylphosphate and the max imum amount of estradiol that could be incorporated. Estradiol saturat ed phosphate buffered saline served as control. Occlusive application of gel state C(18)EO(7)/cholesterol, Wasag-7 or Wasag-15/cholesterol/d icetylphosphate vesicles in phosphate buffered saline increased the es tradiol flux by a factor of 1.5 to 2.4. Occlusive application of liqui d state C(12)EO(7)/cholesterol (1/0.43) or C(12)EO(7)/cholesterol (1/0 .18) vesicles in phosphate buffered saline increased the flux by a fac tor of 4.8 and 9.5, respectively. Occlusive pretreatment with empty C( 12)EO(7)/cholesterol (1/0.18) vesicles, followed by estradiol saturate d phosphate buffered saline, resulted in a 2.9-fold increase in flux. Estradiol loaded C(12)EO(7) micelles exhibited no effect. Occlusive ap plication of C(12)EO(7)/cholesterol (1/0.43) and Wasag-7/cholesterol/d icetyl-phosphate vesicles to Silastic sheeting and stratum corneum wit h the Silastic sheeting facing the donor chamber resulted in a 1.8 to 2.2 higher estradiol flux. The increase in estradiol flux is related t o the flexibility of the bilayers and the encapsulation of estradiol i n vesicles.