Dermal absorption of mucopolysaccharide polysulfate (heparinoid) in human and minipig

Abstract

Dermal absorption of mucopolysaccharide polysulfate (MPS, the active ingredient of Hirudoid®[1)] in human and minipig was investigated by using ¹⁴C-labeled MPS. Three types of human and minipig skin samples were used: intact, dried and tape-stripped. At 24 h after application of ¹⁴C-MPS to intact human skin on a Franz cell in vitro, the radioactivity was detected in 0.98, 1.34, and 0.08% of the applied dose in stratum corneum, epidermal-dermal skin, and receptor fluid, respectively. In dried human skin, the amount of radioactivity detected was similar to that in intact human skin. By contrast, in tape-stripped human skin, higher radioactivity was detected in epidermal-dermal skin and receptor fluid (2.85 and 0.33% of the applied dose, respectively) than in intact or dried skin. Minipig skin showed 1.5 to 4.5 times greater dermal absorption of ¹⁴C-MPS, as compared with human skin. In an in vivo study with minipig, radioactivity was detected at the dosing skin site after dermal administration of ¹⁴C-MPS. The stability of ¹⁴C-MPS in human skin after dermal application was evaluated by agarose gel electrophoresis and ion-exchange chromatography. It was suggested that ¹⁴C-MPS absorbed into human skin would be stable because the chromatogram behaviors of the radioactivity on the two types of method were not shifted. Microautoradiography of human and minipig skins after ¹⁴C-MPS dosing showed that radioactivity was widely distributed in the epidermis in the area near hair follicles. The present results clearly demonstrate that MPS is stable and that a small fraction of it is percutaneously absorbed by human and minipig skin.

Key words

Dermal absorption - Hirudoid® - Microautoradiography - Moisturizer - Mucopolysaccharide polysulfate - Radioisotope

1)

Maruho Co. Ltd., Kyoto, Japan.

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