In vitro and in vivo percutaneous absorption of seleno-L-methionine, an antioxidant agent, and other selenium species

Abstract

Aim: To investigate the in vitro and in vivo percutaneous absorption of seleno-L-methionine (Se-L-M), an ultraviolet (UV)-protecting agent, from aqueous solutions. Methods: Aqueous solutions of Se-L-M were prepared in pH 4, 8, and 10.8 buffers. The pH 8 buffer contained 30% glycerol, propylene glycol (PG) and polyethylene glycol (PEG) 400. The in vitro skin permeation of Se-L-M via porcine skin and nude mouse skin was measured and compared using Franz diffusion cells. The in vivo skin tolerance study was performed, which examined transepidermal water loss (TEWL), skin pH and erythema. Results: In the excised porcine skin, the flux was 0.1, 11.4 and 8.2 μg· cm -2 ·h -1 for the pH 4, 8, and 10.8 buffers, respectively. A linear correlation between the flux and skin deposition was determined. According to permeation across skin with different treatments (stripping, delipidation, and ethanol treatments), it was determined that the intracellular route comprised the predominant pathway for Se-L-M permeation from pH 8 buffer. Aqueous solutions of seleno-DL-methionine (Se-DL-M), selenium sulfide and selenium-containing quantum dot nanoparticles were also used as donor systems. The DL form showed a lower flux (7.0 vs 11.4 μg· cm -2 ·h -1 ) and skin uptake (23.4 vs 47.3 μg/g) as compared to the L form, indicating stereoselective permeation of this compound. There was no or only negligible permeation of selenium sulfide and quantum dots into and across the skin. With in vivo topical application for 4 and 8 h, the skin deposition of Se-L-M was about 7 μg/g, and values were comparable to each other. The topical application of Se-L-M for up to 5 d did not caused apparent skin irritation. However, slight inflammation of the dermis was noted according to the histopathological examination. Conclusion: Se-L-M was readily absorbed by the skin in both the in vitro and in vivo experiments. The established profiles of Se-L-M skin absorption will be helpful in developing topical products of this compound.Keywords: seleno-L-methionine; selenium; percutaneous absorption; topical delivery; skin [5] . In humans, a low selenium status is associated with up to a 4-fold increased risk of developing skin cancer [6] . Topical selenium compounds also increase the minimum dose of UV radiation required to cause skin reddening and protect against skin damage caused by UVB [7,8] . Seleno-L-methionine (Se-L-M), the major component of dietary selenium, represents an organic form of selenium which may provide enhanced protection of the skin [9] . Se-L-M also decreases the oxidative stress of neurodegenerative diseases, rheumatoid arthritis, and HIV/AIDS [10,11] . Most ingested selenium, whether in organic or inorganic form, is converted by liver metabolism [3] . In addition, selenium toxicity can produce gastrointestinal problems [12] . Delivery of pharmacologically active compounds via the skin is an attractive alternative to oral dosing for numerous reasons including stable plasma concentrations, bypass of firstpass effects, and reduction of some si...

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