Skin Penetration Studies Research Articles

In Vitro Percutaneous Penetration: Evaluation of the Utility of Hairless Mouse Skin

The permeability barrier of hairless mouse skin has been determined in vitro after exposure of the epidermal surface to volumes of acetone typically used in human in vivo skin penetration studies. It has been shown that the transport of tritiated water (when applied for limited 5-h periods) across hairless mouse skin is not affected by acetone treatments of approximately 15 microliters/cm2. Submersion of the membranes between aqueous donor and receptor phases for periods greater than 24 h, however, leads to significant and catastrophic barrier impairment. The acetone dose in the experiments reported is greater than that employed in vivo when the solvent is used to deposit a penetrant on human skin. We suggest, therefore, that acetone-mediated facilitation of percutaneous absorption in humans is unlikely. A further conclusion of this work is that in vitro solvent-deposition penetration experiments using hairless mouse skin should provide reliable transport information for at least 48 h postadministration. Although hairless mouse skin is more permeable than its human counterpart, in vitro measurements using the murine barrier should, therefore, provide useful and relevant guidelines for risk assessment calculations and bioavailability determinations.

An automated method for continuously monitoring diffusion cells in skin penetration studies

A fully automated system for studying in vitro skin penetration has been developed. In the present system, frequent monitoring of drug transport through a membrane in a diffusion cell provides for the accurate measurement of steady-state flux and lag time, which is often difficult to monitor using conventional systems because of infrequent sampling. Each diffusion cell is connected to a micro flow cell in the spectrophotometer and the receptor cell fluid continuously flows through the micro flow cell back into the receptor cell due to the pressure caused by stirring inside the diffusion cell. This strirring also ensures mixing inside the receptor cell. The spectrophotometer is controlled by a personal computer so that drug penetration through the membrane can be monitored continuously because of frequent UV absorbance measurements. The usefulness of the system has been verified using shed snake skin as a model membrane.

The effect of skin penetration enhancers on the transdermal delivery of pyridostigmine bromide

AbstractIn vitro skin penetration studies of pyridostigmine bromide through human cadaver skin were conducted using a diffusion cell with constant hydrodynamic conditions. The results indicate that the drug penetrates poorly through human cadaver skin. However, skin penetration enhancers such as sodium oleate, sodium lauryl sulfate, n-decyl methyl sulfoxide, and N,N-dimethyldodecylamine-N-oxide substantially enhanced the permeability coefficient of the drug through human cadaver skin. The penetration enhancement of pyridostigmine bromide could be due to increased partitioning of the drug in the skin or due to the decreased tortuosity of the porous pathway in the stratum corneum.

Membrane models for skin penetration studies

Membrane models for skin penetration studies

Systemic toxicity from subchronic dermal exposure, chemical characterization, and dermal penetration of catalytically cracked clarified slurry oil.

Clarified slurry oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 male and 10 female Sprague-Dawley rats 5 days/week for 13 weeks at doses of 8, 30, 125, or 500 mg/kg/day, and to another group for 2 weeks at doses of 2000 mg/kg/day. The rats were fitted with cardboard Elizabethan collars to minimize the ingestion of the test material, which was applied undiluted and remained uncovered on the skin. A similar group of rats served as controls; they were treated in the same manner except that no CSO was applied to their skin. There was a dose-related mortality and depression of body weight gain in the rats treated with CSO at doses of 30 mg/kg/day or greater; none of the rats dosed at 2000 mg/kg/day survived more than 2 weeks. The primary target organs of CSO toxicity were the liver, thymus, and bone marrow. The effects on the liver included increased weight (250% at 500 mg/kg/day), cholangiolitis, diffuse liver cell degeneration and hypertrophy, necrosis, fibrosis, decreased serum glucose, increased levels of alkaline phosphatase, aspartate aminotransferase, alanine amino transferase, bilirubin, and triglycerides. The thymus was found to be small and upon microscopic examination to be atrophic or hypoplastic. Erythroid hypoplasia was found in the bone marrow of some of the rats dosed at 30 mg/kg/day and increased in severity with increasing dose. The erythroid hypoplasia was accompanied by a dose-related anemia. Even in the rats dosed at 8 mg/kg/day, very slight abnormalities in the bile ducts were observed upon microscopic examination of the liver. Chromatographic separation and analyses demonstrated that CSO contains about 58% 3- to 5-ring polycyclic aromatic hydrocarbons (PAHs) and approximately 8-10% carbazole derivatives. In vitro and in vivo skin penetration studies demonstrated that the carbazole materials penetrate through the skin to a considerable extent (about 44%); less penetration was observed with 2- or 3-ring (8-13%) or 5-ring PAHs (3%).

Cosmetic ingredients go further than skin deep: Marzulli F.N., Anjo D.M. & Maibach H.I. (1981). In vivo skin penetration studies of 2,4-toluenediamine, 2,4-diaminoanisole, 2-nitro- p-phenylenediamine, p-dioxane and N-nitrosodiethanolamine in cosmetics. Fd Cosmet. Toxicol. 19, 743.

Cosmetic ingredients go further than skin deep: Marzulli F.N., Anjo D.M. & Maibach H.I. (1981). In vivo skin penetration studies of 2,4-toluenediamine, 2,4-diaminoanisole, 2-nitro- p-phenylenediamine, p-dioxane and N-nitrosodiethanolamine in cosmetics. Fd Cosmet. Toxicol. 19, 743.

Secondary ion emission microanalysis: applications to the study of human skin.

Secondary ion emission microanalysis is a new method of physical analysis recently applied in biology. The apparatus required (CAMECA SMI 300) enables pictures to be taken of the distribution of certain elements, with a space resolution of the order of 1 microgram. Concentrations below 1 p.p.m. are perceptible for most elements. The present results are the first obtained for human skin sections. Investigation of the natural elements of normal skin reveals no particular accumulation. Elements foreign to the skin are easy to detect. We show here the distribution in the epidermis of clinical antiseptics applied locally. This method has two advantages compared to X-ray microanalysis. It is more sensitive and allows analysis of even the lightest elements. However, its use in skin penetration studies is limited because it does not permit quantitative analysis and serious interference problems may occur.