Topical delivery of silymarin constituents via the skin route

Abstract

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 approximately 4.0- and 30 approximately 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.

Figure 1

Chemical structures of silibinin (SB), silydianin (SD), and silychristin (SC).

Figure 2

Cumulative amount versus time profiles of in vitro topical silibinin (SB) application permeating across nude mouse skin from aqueous buffers with different pH values. n=4. Mean±SD.

Figure 3

The permeability coefficient (K_p) (A) and in vitro calibrated skin deposition (B) of silibinin (SB), silydianin (SD), and silychristin (SC) from pH 8 and 9 buffers across intact or UVB-irradiated skin. n=4. Mean±SD. ^bP<0.05 vs pH 8/intact skin.

Figure 4

Images of nude mouse skin before and after UVB irradiation for 7 d: (A) clinical observation before UVB irradiation; (B) clinical observation after UVB irradiation; (C) COX-2 expression by immunochemical staining before UVB irradiation, ×400; (D) COX-2 expression by immunochemical staining after UVB irradiation, ×400; (E) PCNA expression by immuno-chemical staining before UVB irradiation, ×400; (F) PCNA expression by immunochemical staining after UVB irradiation, ×400.

Figure 5

In vivo skin irritation examination determined by transepidermal water loss (TEWL), erythema (a*), and the pH value after a 24-h application of topically applied silibinin (SB), silydianin (SD), and silychristin (SC) from pH 8 buffer. The Δ value indicates the value of the treated site minus the value of an adjacent untreated site. n=6. Mean±SD.

Figure 6

The stereo structure of silibinin (SB), silydianin (SD), and silychristin (SC) pictured by a molecular modeling software (Discovery Studio^® version 2.0, Accelrys Inc, San Diego, USA).