Application of vesicles to rat skin in vivo: a confocal laser scanning microscopy study

A major problem in (trans)dermal drug delivery is the low penetration rate of most substances through the barrier of the skin, the stratum corneum. On e of the methods to increase the penetration rate across the skin is encaps ulation of a (model) drug in lipid vesicles. In this study fluorescently la belled liposomes were applied on rat skin, in vivo. Bilayer labelled gel-st ate and liquid-state liposomes (conventional or with flexible bilayers) wer e non-occlusively applied on the dorsal area in the neck of the rat for 1, 3 or 6 h. Micelles were used as a control formulation. The penetration path way and penetration depth of the lipophilic fluorescent label into the skin was visualised by confocal laser scanning microscopy (CLSM), During the fi rst 3 h of application almost no differences in penetration depth were obse rved, when the label was applied in the various formulations. After 6 h app lication, it was clear that the label applied in micelles and gel-state lip osomes did not penetrate as deep into the skin as the label applied in liqu id-state vesicles. Among the liquid-state vesicles, the suspension with the most flexible bilayers showed the highest fluorescence intensity in the vi able epidermis and dermis, 6 h post-application, Thus the vesicular form an d the thermodynamic state of the bilayer and to a smaller extent the flexib ility of the bilayer influence the penetration depth of the label into the skin at longer application periods. These results are in good agreement wit h CLSM results obtained from in vitro experiments with human skin. (C) 1998 Elsevier Science B.V. All rights reserved.