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Biomedical subjects

J L Lichtin

Publications and source records attributed to J L Lichtin.

5 recordsLinked to original sources

Characterization of esterase and alcohol dehydrogenase activity in skin. Metabolism of retinyl palmitate to retinol (vitamin A) during percutaneous absorption.

Retinyl palmitate, a widely used ingredient in cosmetic products, is promoted for its beneficial effects on the appearance of skin. Previous studies suggest that enzymes are available in skin to metabolize this ingredient during skin absorption. Esterase activity hydrolyzes retinyl palmitate to retinol (vitamin A), which is oxidized in many tissues to retinoic acid primarily by alcohol dehydrogenase. The activities of esterase and alcohol dehydrogenase were characterized in hairless guinea pig skin by using flow-through diffusion cells and radiolabeled model compounds (methyl salicylate and benzyl alcohol) previously shown to be metabolized by these enzymes. Methyl salicylate was hydrolyzed by esterase to a greater extent in viable skin than in nonviable skin. Glycine conjugation of salicylic acid and benzoic acid occurred only in viable skin. The metabolism of methyl salicylate and benzyl alcohol occurred to a greater extent in male guinea pig skin than in female guinea pig skin. The percutaneous absorption of both radiolabeled compounds was similar in viable and nonviable skin. About 30 and 18% of topically applied retinyl palmitate were absorbed from an acetone vehicle by hairless guinea pig skin and human skin, respectively. Less than 1% of the applied dose of this lipophilic compound diffused from skin into the receptor fluid. Retinol was the only detectable metabolite of retinyl palmitate in both hairless guinea pig and human skin. In human skin, 44% of the absorbed retinyl palmitate was hydrolyzed to retinol. The use of retinyl palmitate in cosmetic formulations may result in significant delivery of retinol into the skin.

Alcohol Dehydrogenase

In vitro skin absorption and metabolism of benzoic acid, p-aminobenzoic acid, and benzocaine in the hairless guinea pig.

The percutaneous absorption and metabolism of three structurally related compounds, benzoic acid, p-aminobenzoic acid (PABA), and ethyl aminobenzoate (benzocaine), were determined in vitro through hairless guinea pig skin. Benzocaine was also studied in human skin. Absorption of benzocaine was rapid and similar through both viable and nonviable skin. The absorption of the two acidic compounds, benzoic acid and PABA, was greater through nonviable skin. A small portion (6.9%) of absorbed benzoic acid was conjugated with glycine to form hippuric acid. Although N-acetyl-benzocaine had not been observed as a metabolite of benzocaine when studied by other routes of administration, both PABA and benzocaine were extensively N-acetylated during percutaneous absorption. Thus, the metabolism of these compounds should be considered in an accurate assessment of absorption after topical application.

4-Aminobenzoic Acid

Maintenance of skin viability during in vitro percutaneous absorption/metabolism studies.

The assessment of cutaneous metabolism during in vitro percutaneous absorption studies requires maintenance of the viability of the skin section. With the use of flowthrough diffusion cells, Eagle's minimal essential medium (MEM), Hepes-buffered Hanks' balanced salt solution (HHBSS), or Dulbecco modified phosphate-buffered saline (DMPBS), acting as receptor fluids, were able to sustain aerobic and anaerobic glucose utilization, testosterone and estradiol metabolism, and histopathological appearance of perfused rat skin sections for 24 hr. Fetal bovine serum supplements were not required for survival and appeared to inhibit the extraction of the metabolite estrone from the receptor fluid fractions in estradiol absorption/metabolism experiments. The use of phosphate-buffered saline (PBS) resulted in elimination of aerobic and anaerobic glucose utilization in 12 hr and declining appearance of steroid metabolites in receptor fluid fractions during the 24-hr percutaneous absorption/metabolism studies. Histopathological examination of skin sections perfused with PBS for 24 hr showed autolysis of the viable epidermis and dermis. The results demonstrate that an appropriate receptor fluid, such as MEM, HHBSS, or DMPBS, is required for percutaneous absorption studies in which cutaneous metabolism of the penetrating compound is to be considered.

Analysis of Variance

Assay of mixtures of padimate-O and oxybenzone in sunscreen formulations by high-performance liquid chromatography.

A simple assay method for the quality control of some sunscreen products containing padimate-O and oxybenzone has been developed. A methanolic extract of the product containing sulfathiazole internal standard was subjected to reversed-phase high-performance liquid chromatography on a 10-micron Partisil ODS-2 column with methanol-acetonitrile (90:10, v/v) mobile phase. The drug-sulfathiazole peak height ratio was linear between 0.04-2.68 micrograms of padimate-O (r = 1.0003) and 0.02-1.05 micrograms of oxybenzone (r = 0.9997) injected. All peaks were well-resolved. Approximate retention times for sulfathiazole, oxybenzone and padimate-O were 3.9, 5.7 and 7.4 min., respectively. The height equivalent to a theoretical plate (+/- S.D.) were (n = 10) 0.79 +/- 0.07, 0.53 +/- 0.06 and 0.26 +/- 0.04 mm, for sulfathiazole, oxybenzone and padimate-O, respectively. Average percent recoveries (+/- S.D.) (n = 3) from simulated lotions containing 7% padimate-O and 3% oxybenzone were: padimate-O, 101.4 +/- 1.5%; oxybenzone 99.9 +/- 1.9%; from simulated lipsticks containing (a) 7% padimate-O and 3% oxybenzone: 103.8 +/- 1.2% and 100.1 +/- 0.9%, respectively; and (b) 7% padimate-O and 0.5% oxybenzone: 99.4 +/- 0.6% and 99.3 +/- 2.4%, respectively. The method was successfully applied to marketed products.

4-Aminobenzoic Acid