Permeation of the human skin by heparin and mucopolysaccharide polysulfuric acid ester.

ABSTRACT

Punched samples of different specimens of human skin were treated with 5 mg/cm2 of commercially available topical preparations of heparin (50,000 IU/100 g, i.e. 0.35% w/w) or mucopolysaccharide polysulfuric acid ester (MPS, 1.4 and 0.45% w/w, respectively; active ingredient of Hirudoid). Heparin and MPS were labelled with tritium. The skin samples were fixed into a perfusion chamber. Perfusion fluid and skin were analysed 180 to 360 min later. The concentrations found in the corium varied from 0.005 to 0.1 IU heparin per g (i.e. 0.03 to 0.64 micrograms/g) and from 1.05 to 3.14 micrograms/g of MPS. While in normal skin the single administration of heparin and MPS resulted in levels of the same relative magnitude, skin with thinner epidermis and decreased horny layer (keloids) absorbed MPS to a higher degree. Repeated administration of a 1.4% MPS cream (0 and 90 min, measurement after 180 min) resulted in markedly enhanced levels, which were out of proportion especially in the deeper skin layers. This effect was confirmed with a 0.45% MPS cream. The direct comparison to the heparin cream resulted in higher heparin levels in the epidermis but higher MPS levels in all deeper skin layers, when calculated to the same concentration in the cream. The heparin in the dermal layers and in the perfusion chamber fluid was determined by molecular binding to protamine loaded sepharose 4B.