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Int J Pharm. 2008 Apr 16;354(1-2):180-95. Epub 2007 Aug 25.

Interaction of lipid nanoparticles with human epidermis and an organotypic cell culture model.

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Department of Pharmaceutics, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland.


Various lipid nanoparticle formulations were investigated with respect to (trans)dermal drug delivery with special regard to the mechanism of their effects on human and an organotypic cell culture epidermis. Potential alterations of stratum corneum lipid domains were studied using fluorescence assays with labeled liposomes and thermal analysis of isolated stratum corneum. Influences on the permeation of corticosterone were investigated and the occlusive properties of the nanoparticles were determined by measurements of the transepidermal water loss (TEWL). The penetration of a fluorescence dye was visualized by fluorescence microscopy of cross sections of human epidermis after incubation with cubic and solid lipid nanoparticles. Corticosterone permeation was limited when applied in matrix-type lipid nanoparticles (fat emulsion, smectic and solid lipid nanoparticles). An adhesion of solid lipid nanoparticles was clearly observed in thermal analysis as reflected by additional phase transitions probably caused by the nanoparticle matrix lipid. However, as for the other matrix-type nanoparticles, no distinct alterations of the phase transitions of the stratum corneum lipids were observed. Cubic nanoparticles led to the most predominant effect on skin permeation where the surface-active matrix lipid may act as penetration enhancer. An alteration of the stratum corneum lipids' thermal behavior as well as an interaction with fluorescence labeled liposomes was observed. Differences observed in permeation studies and thermal analysis of human and cell culture epidermis indicate that surface lipids, which are not present to the same extent in the cell culture model than in human epidermis, seem to play an important role.

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