Skin delivery of oestradiol from lipid vesicles: importance of liposome structure

The aim of this study was to investigate the importance of liposome structure in oestradiol skin delivery as a tool for understanding the delivery mechanism from lipid vesicles. Liposomes of phosphatidylcholine (PC) (1),PC, sodium cholate; 86:14 w/w (II), PC, Span 80; 86.7:13.3 w/w (III) and PC, oleic acid; 84:16 w/w (IV) with 1 mg/ml radiolabelled drug were prepared. Saturated radiolabelled oestradiol solutions containing the components of I-IV were separately prepared in 90%, w/w propylene glycol in water. In addition, saturated solutions containing cholate, Span, oleic acid and ethanol at the same concentrations used in vesicles wt:re formulated. Oestradiol permeation through human epidermis was studied. Formulations I-IV increased oestradiol flux by 8.6, 17, 17 and 13-fold when used as vesicles compared with control and by 2.9, 4.0, 4.7 and 6.9-fold when used in solution with drug. Testing individual components in solution, relative fluxes were 2.9, 0.87, 1.1, 2.9 and 1.1 for PC, cholate, Span, oleic acid and 7% ethanol, respectively. Accordingly, it is important to prepare phospholipids as vesicles for efficient oestradiol skin delivery even after inclusion of oleic acid. Penetration enhancement is not the main mechanism for improved flux. Liposome components in solution have additive effect with a possible synergism in some cases. (C) 2000 Elsevier Science B.V. All rights reserved.