Puri A, Nguyen H X, Banga A K
Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA, 30341, USA.
Int J Cosmet Sci. 2016 Oct;38(5):512-23. doi: 10.1111/ics.12320. Epub 2016 Apr 22.
Epigallocatechin-3-gallate (EGCG) is the physiologically most active and abundant flavanol, accounting for 50-80% of green tea catechins. It is an anti-inflammatory, antioxidant, chemopreventive and skin photoprotective agent. However, light sensitivity and low permeability of EGCG across the stratum corneum due to its high molecular weight as well as strong binding to the lipid bilayers in the skin make it difficult to be used as a key ingredient in cosmetic products. This study aimed to formulate a photostable hydrogel of EGCG with good rheological properties for dermal application and investigate the effect of skin microporation using maltose microneedles on its permeation through dermatomed porcine skin.
Effect of l-glutathione on photodegradation of EGCG was investigated by exposing samples to ultraviolet irradiation for 1 h using a solar simulator. Hydrogels with varying concentrations of Carbopol 980 (0.5-2% w/v) as an gelling agent were prepared, and their rheological properties were evaluated using a rheometer. Skin microporation was confirmed by assessing the skin resistance, transepidermal water loss and calcein imaging of the microchannels created by the microneedles. Permeation of EGCG from aqueous solution as well as the rheologically optimized hydrogel through the dermatomed porcine skin (untreated and microneedle treated) was evaluated using static vertical Franz diffusion cells.
l-glutathione acting as a co-antioxidant and photostabilizer significantly (P < 0.05) reduced the degradation of EGCG from 21.53 ± 2.78% to 1.0 ± 0.68% after 1 h of ultraviolet irradiation. Rotational and oscillatory rheological tests indicated that the hydrogel containing 1.5% Carbopol 980 is acceptable for topical application in terms of flow behaviour, elasticity, spreadability, structural stability and thixotropy. Microneedle-treated skin showed significant enhancement (P < 0.05) in the delivery of EGCG to viable epidermis and dermis from the aqueous solution (38.67 ± 2.96 μg cm(-2) ) as well as hydrogel (24.60 ± 2.62 μg cm(-2) ) in comparison with the untreated skin (24.16 ± 2.11 and 15.62 ± 0.24 μg cm(-2) for aqueous solution and hydrogel, respectively).
Addition of glutathione in EGCG formulations significantly reduces its photodegradation. Skin microporation with maltose microneedles facilitates the penetration of EGCG across the stratum corneum into the deeper skin layers - viable epidermis and dermis.
表没食子儿茶素-3-没食子酸酯（EGCG）是生理活性最强且含量最丰富的黄烷醇，占绿茶儿茶素的50 - 80%。它是一种抗炎、抗氧化、化学预防和皮肤光保护剂。然而，由于其高分子量以及与皮肤脂质双分子层的强结合性，EGCG在角质层的光敏感性和低渗透性使其难以用作化妆品的关键成分。本研究旨在制备一种具有良好流变学性质的EGCG光稳定水凝胶用于皮肤应用，并研究使用麦芽糖微针进行皮肤微孔化对其透过离体猪皮肤渗透的影响。
通过使用太阳模拟器将样品暴露于紫外线照射1小时，研究L-谷胱甘肽对EGCG光降解的影响。制备了含有不同浓度（0.5 - 2% w/v）卡波姆980作为凝胶剂的水凝胶，并使用流变仪评估其流变学性质。通过评估微针形成的微通道的皮肤电阻、经表皮水分流失和钙黄绿素成像来确认皮肤微孔化。使用静态垂直弗兰兹扩散池评估EGCG从水溶液以及流变学优化的水凝胶透过离体猪皮肤（未处理和微针处理）的渗透情况。
作为共抗氧化剂和光稳定剂的L-谷胱甘肽在紫外线照射1小时后显著（P < 0.05）降低了EGCG的降解，从21.53 ± 2.78%降至1.0 ± 0.68%。旋转和振荡流变学测试表明，含有1.5%卡波姆980的水凝胶在流动行为、弹性、铺展性、结构稳定性和触变性方面适合局部应用。与未处理的皮肤相比（水溶液和水凝胶分别为24.16 ± 2.11和15.62 ± 0.24 μg cm(-2)），微针处理的皮肤在将EGCG从水溶液（38.67 ± 2.96 μg cm(-2)）以及水凝胶（24.60 ± 2.62 μg cm(-2)）递送至活表皮和真皮方面显示出显著增强（P < 0.05）。
在EGCG制剂中添加谷胱甘肽可显著降低其光降解。使用麦芽糖微针进行皮肤微孔化有助于EGCG穿过角质层渗透到更深的皮肤层——活表皮和真皮。
