Lipids from hairless mouse skin

Particles from cationic lipids may also be useful for antisense therapy of skin disease — a nontoxic increase in the oligonucleotide uptake by cultivated keratinocytes and a sebocyte cell line has been reported [66]. Moreover, cationic dendri-mers also efficiently transfer reporter gene DNA to human keratinocytes cultivated in vitro. In the skin of hairless mice, in vivo transfection was possible with complexes, yet reporter gene expression was localized to perifollicular areas. Transfection, however, failed with the naked plasmid. For prolonged contact, biodegradable membranes coated with dendrimer/DNA complexes were used [67]. This hints at a follicular uptake of these complexes and indicates that gene transfection also may be possible with human skin, which has a thicker stratum comeum compared with mouse skin (eight to ten vs. two to three layers [58]). 

In this chapter we summarize work from our laboratory in which we have tested these predictions. The hairless mouse is our model. Initial experiments utilized excised skin while later studies used an in vivo system. We irradiated these systems with either UVA (320 100 nm), UVB (290-320 nm), or simulated sunlight in a pattern of UVA and UVB which closely matched natural sunlight. We have measured UV-induced changes in antioxidants, lipid peroxidation, and the effects of dietary supplementation with the major chain-breaking lipophilic antioxidant, a-tocopherol, on UV-induced skin damage. 

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