Electrical resistance and tritiated water permeability as indicators of barrier integrity of in vitro human skin

Abstract

The use of human skin for percutaneous penetration studies invariably involves storage of tissue prior to use, and assessment of barrier integrity is important as damage to the skin may occur during surgical removal, storage, or technical preparation. This assessment is frequently performed by measurement of skin permeability to marker chemicals, but measurement of electrical resistance is a recently proposed alternative technique. Epidermal membranes or full-thickness abdominal and mammary skin were mounted in static glass diffusion cells and electrical resistance of hydrated skin was measured before (‘pre’) and after (‘post’) performance of a tritiated water permeability study. A linear relationship was evident between the water permeability coefficient ( K p) and absorption of tritiated water. The majority of skin preparations displaying intact barrier integrity, as defined by tritiated water permeability, had an initial electrical resistance of at least 45.4 kΩcm 2 and a post-permeability study resistance greater than 20 kΩcm 2. Membrane resistance selection criteria for an intact barrier integrity were applied to skin absorption data for [ 14C]mannitol and the calculated mean K p value was in good agreement with published values. Interindividual variation was evident, but the permeability coefficients for tritiated water and mannitol were similar for epidermal membranes and full-thickness skin prepared from abdominal skin of male or female donors or for mammary skin. Electrical resistance provided a rapid assessment of barrier integrity and was applicable to epidermal membranes and full-thickness human abdominal and mammary skin.