Skin Penetration by Phospholipid Vesicles, Transfersomes,
As Visualized by Means of the Confocal Laser Scanning Microscopy
A. Schätzlein *+ and G. Cevc*
*Medizinische Biophysik, Klinikum r.d.I., Ismaningerstraße
22,
Technische Universität München, 81635 München, EU
+IDEA GmbH, Frankfurter Ring 193a, 80807-München, EU;
In: Phospholipids: Characterization, Metabolism and Novel
Biological Applications (G. Cevc, F. Paltauf, eds.) AOCS Press, Champain,
IL, 1995, pp 191-209.
The intact skin is a highly efficient penetration obstacle
to the epicutaneous drug and particle administration. Its main permeability
barrier is located in the stratum corneum, the surface layer of the epidermis.
Innovative, ultradeformable drug carriers, Transfersomes, which can be
made on the basis of phospholipids, can overcome this penetration barrier,
however, Here we exploit the technique of the confocal laser scanning
microscopy (CLSM) to show this and to elucidate the route of the Transfersome
entry into the murine skin. We demonstrate that the fluorescently labelled
transfersomes may take advantage of the structural irregularities in the
micro-anatomy of the stratum corneum (`virtual pores') in order to get
into the skin. The resulting pathway corresponds to a three-dimensional
network of the intercellular passages between the corneocytes. In contrast
to liposomes and micelles, which can only reach the upper parts of the
stratum corneum, transfersomes can get deep into the epidermis and beyond.
Within a few hours time, an increasing amount of the Transfersome-associated
fluorescence is even found in the dermis. For the double labelled transfersomes,
the penetration depth, the pathways, and the tissue distribution, as well
as the fluorescence intensity at various depths in the skin are practically
identical for both labels. This suggests that transfersomes do not solubilise
the stratum corneum lipids or else fall apart in the skin. Such bodies
must thus penetrate through the skin barrier as well preserved (but probably
strongly deformed) entities. Experiments in nude mice or hairy mice yield
essentially identical results. Skin penetration via the hair follicles
thus only plays a minor role for transfersomes, but may be of great importance
for the liposome or mixed micelle penetration into the intact skin.
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