J. Akimoto et al., EVALUATION OF SKIN IRRITATION OF PERCUTANEOUS-ABSORPTION PROMOTERS BYMEANS OF FRACTAL DIMENSION OF RAT SKIN-STRUCTURE, International journal of pharmaceutics, 128(1-2), 1996, pp. 251-260
A fractal dimension of skin structure was determined in order to evalu
ate tl-e pathological damages evoked by percutaneous absorption promot
ers such as d-limonene and Atone in the hairless rat. As a model derma
tological system, indomethacin hydrogels containing each of these enha
ncers were applied to the hairless rat abdominal skin. The application
site of the skin was excised, fixed with glutaraldehyde and osmic aci
d, and then lyophilized. Boundary lines between the outermost lipid la
yer and the underlying protein parts in the skin cross section were ta
ken by the CCD camera as image data, and these images were fed into a
computer to estimate the fractal dimension. The boundary line of the s
kin cross section was observed to be a typical fractal morphology and
the structure changes of skin evoked by the promoters could be quantif
ied as a non-integral fractal dimension. A linear relationship between
the fractal dimension and pathological irritation score was clearly o
bserved, suggesting the usefulness and reliability of the fractal dime
nsion as a novel method for evaluating the skin damage.