Acta Pharmacologica Sinica (2010) 31: 118–126; doi: 10.1038/aps.2009.186; published online 21 December 2009

Chi-feng HUNG¹, Yin-ku LIN², Li-wen ZHANG³, Ching-hsien CHANG², Jia-you FANG^3,*

¹School of Medicine, Fu Jen Catholic University, Taipei County, Taiwan, China; ²Department of Traditional Chinese Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan, China; ³Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan, China

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<SD<SB.  Increased lipophilicity of a compound resulted in higher skin deposition but had a minor effect on permeation across the skin in the less-ionized form (pH 8).  It is apparent that compounds in the less-ionized form showed higher skin uptake compared to the more-ionized form.  Hyperproliferative skin produced by UVB exposure showed increased permeation of silymarin constituents in the less-ionized form, but it did not affect deposition within the skin.  With in vivo topical application for 4 and 8 h, the skin deposition of SB was higher than those of SD and SC by 3.5~4.0- and 30~40-fold, respectively.  The skin disruption and erythema test demonstrated that the topical application of these compounds for up to 24 h caused no apparent skin irritation.

Conclusion: The basic profiles of silymarin permeation via skin route were established.

Keywords: silymarin; silibinin; skin; topical delivery; ultraviolet B; permeation; absorption