Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok, 65000, Thailand.
Cosmetics and Natural Products Research Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, 65000, Thailand.
Drug Deliv Transl Res. 2018 Feb;8(1):140-149. doi: 10.1007/s13346-017-0447-7.
Minoxidil is approved for topical treatment of androgenic alopecia but hampered by poor cutaneous absorption. Recently, the randomized control trial showed that hair loss treatment of minoxidil was improved by co-application of the anti-androgen, Curcuma aeruginosa Roxb. extract. Here, we aimed to show that the apparent synergism arises from improved cutaneous penetration of minoxidil by bioactive compound, germacrone or C. aeruginosa (as an n-hexane extract, or essential oil). The partition coefficient of germacrone was determined by HPLC. Skin penetration was measured ex vivo on Franz diffusion cells using full thickness human foreskin as membranes. The receiver solution was sampled hourly for 8 h after which the skin was removed, the stratum corneum separated, and minoxidil assayed in this and in the remaining viable skin layer by HPLC. Skin penetration of minoxidil with 0.2 and 2% extract was increased ~ 4-fold (accumulated amount in receiver + skin viable layer after 8 h). Furthermore, germacrone enhanced minoxidil flux by ~ 10-fold and C. aeruginosa essential oil by ~ 20-fold. This work suggests three clinical consequences: (i) minoxidil efficacy is promoted, (ii) lower doses of minoxidil suffice, and (iii) C. aeruginosa extract/essential oil or germacrone can supplement treatment outcomes by acting as anti-androgen, thereby introducing a more effective topical treatment strategy for androgenic alopecia.
米诺地尔被批准用于治疗雄激素性脱发的局部治疗，但由于皮肤吸收不良而受到限制。最近，一项随机对照试验表明，将姜黄提取物与抗雄激素药物联合应用可改善米诺地尔的脱发治疗效果。在这里，我们旨在表明，协同作用源于生物活性化合物，倍半萜烯或姜黄（作为正己烷提取物或精油）对米诺地尔的皮肤穿透性的改善。通过 HPLC 确定倍半萜烯的分配系数。使用完整厚度的人体包皮作为膜，在 Franz 扩散细胞上进行离体皮肤穿透性测量。在 8 小时后，每隔 1 小时从接收器溶液中取样，然后去除皮肤，分离角质层，并通过 HPLC 测定该层和剩余的有活力皮肤层中的米诺地尔含量。0.2%和 2%提取物的米诺地尔皮肤穿透性增加了约 4 倍（8 小时后接收器+皮肤有活力层中的累积量）。此外，倍半萜烯将米诺地尔通量提高了约 10 倍，姜黄精油提高了约 20 倍。这项工作提出了三个临床后果：（i）促进了米诺地尔的疗效，（ii）足够低的米诺地尔剂量即可，（iii）姜黄提取物/精油或倍半萜烯可以作为抗雄激素剂来补充治疗效果，从而为雄激素性脱发引入了更有效的局部治疗策略。
