Transdermal skin delivery: Predictions for humans from in vivo, ex vivo and animal models☆

Godin, Biana; Touítou, Elka

doi:10.1016/j.addr.2007.07.004

Cited by 566 publications

(371 citation statements)

References 72 publications

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“…The skin of rodents is most commonly used for in vitro and in vivo skin permeation studies. There are a number of hairless species (eg, nude mice and hairless rats) in which the absence of a hairy coat mimics human skin better than hairy skin [19] . Hence nude mice were also utilized as an animal model in this study.…”

Section: Discussionmentioning

confidence: 99%

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

Lin

Fang²,

Al‐Suwayeh

et al. 2011

Acta Pharmacol Sin

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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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Section: Discussionmentioning

confidence: 99%

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

Lin

Fang²,

Al‐Suwayeh

et al. 2011

Acta Pharmacol Sin

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show abstract

“…The skin of rodents is most commonly used for in vitro and in vivo skin permeation studies. There are a number of hairless species (eg, nude mice and hairless rats) in which the absence of a hairy coat mimics the human skin better than hairy skin [15] . Hence nude mice were used as an animal model in this study.…”

Section: In Vitro Skin Absorption Across Uvb-irradiated Skinmentioning

confidence: 99%

Topical delivery of silymarin constituents via the skin route

et al. 2009

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Aim: Silibinin (SB), silydianin (SD), and silychristin (SC) are components of silymarin. These compounds can be used to protect the skin from oxidative stress induced by ultraviolet (UV) irradiation and treat it. To this end, the absorption of silymarin constituents via the skin was examined in the present report. Methods: Transport of SB, SD, and SC under the same thermodynamic activity through and into the skin and the effects of pH were studied in vitro using a Franz diffusion assembly. Results: The lipophilicity increased in the order of SC

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“…Because mouse and macaque skin have a higher density of hair follicles than human skin and a different thickness when compared with human skin (Godin and Touitou, 2007), direct translation of vaccination protocols to clinical application is difficult. To prepare for the use of DNA tattoo vaccination in a phase 1 clinical trial, we have therefore developed an ex vivo human skin model that allows the measurement of vaccine-induced gene expression in real time.…”

mentioning

confidence: 99%

Optimization of Intradermal Vaccination by DNA Tattooing in Human Skin

et al. 2009

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The intradermal administration of DNA vaccines by tattooing is a promising delivery technique for genetic immunization, with proven high immunogenicity in mice and in nonhuman primates. However, the parameters that result in optimal expression of DNA vaccines that are applied by this strategy to human skin are currently unknown. To address this issue we set up an ex vivo human skin model in which DNA vaccine-induced expression of reporter proteins could be monitored longitudinally. Using this model we demonstrate the following: First, the vast majority of cells that express DNA vaccine-encoded antigen in human skin are formed by epidermal keratinocytes, with only a small fraction (about 1%) of antigen-positive epidermal Langerhans cells. Second, using full randomization of DNA tattoo variables we show that an increase in DNA concentration, needle depth, and tattoo time all significantly increase antigen expression ( p < 0.001), with DNA concentration forming the most critical variable influencing the level of antigen expression. Finally, in spite of the marked immunogenicity of this vaccination method in animal models, transfection efficiency of the technique is shown to be extremely low, estimated at approximately 2 to 2000 out of 1Â10 10 copies of plasmid applied. This finding, coupled with the observed dependency of antigen expression on DNA concentration, suggests that the development of strategies that can enhance in vivo transfection efficacy would be highly valuable. Collectively, this study shows that an ex vivo human skin model can be used to determine the factors that control vaccine-induced antigen expression and define the optimal parameters for the evaluation of DNA tattoo or other dermal delivery techniques in phase 1 clinical trials.

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Transdermal skin delivery: Predictions for humans from in vivo, ex vivo and animal models☆

Cited by 566 publications

References 72 publications

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

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

Topical delivery of silymarin constituents via the skin route

Optimization of Intradermal Vaccination by DNA Tattooing in Human Skin

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