Electrically assisted skin delivery of liposomal estradiol; phospholipid as damage retardant

This work investigated transdermal penetration of a model lipophilic drug (estradiol) through human epidermis from phosphatidylcholine (PC)-based liposomes and saturated aqueous estradiol solution (control). Representative examples of cholate-containing ultradeformable (Transfersomes), non-rigid (pure PC) and membrane-stabilized (cholesterol-containing) vesicles were used. The unilamellar vesicles' diameters and zeta potentials were determined. Transdermal penetration studies involved occluded passive penetration for 12 h and cathodic iontophoresis (0.8 mA/cm(2)) for 8 h for all systems. Combined electroporation (5 pulses, 100 V, 100 ms, 1 min spacing) and iontophoresis (0.8 mA/cm2, for 2 h) was also employed for ultradeformable vesicles and control. Estradiol penetration parameters (flux and skin deposition) from different formulations were compared. All vesicles had essentially the same particle size, with ultradeformable liposomes showing the highest negative zeta potential (-29 mV). Occluded passive penetration improved estradiol skin penetration from liposomes relative to control. Iontophoretic studies revealed the superiority of ultradeformable vesicles regarding drug skin penetration and deposition compared to traditional liposomes. Combination of electroporation and iontophoresis did not markedly improve estradiol penetration for ultradeformable vesicles. The combination results implied repair of the skin barrier due to the penetration retarding effect of PC monomers released from liposomes. (C) 2004 Elsevier B.V. All rights reserved.