Yu Meng, Guo Fang, Ling Ying, Li Nan, Tan Fengping
a Tianjin Key Laboratory of Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology , Tianjin University , Tianjin , PR China.
Drug Deliv. 2015 Dec;22(8):1053-1058. doi: 10.3109/10717544.2013.869276. Epub 2013 Dec 13.
This study was to investigate the topical skin targeting effects and mechanism of combination penetration modifiers of 1,2-hexanediol (or 1,2-heptanediol) and 1,4-cyclohexanediol on transdermal absorption of metronidazole (MTZ) in different skin models.
Six formulations were applied to pig abdominal skin and pig ear skin models, respectively, and the results were compared with the previous data on hairless mouse skin worked out by our laboratory. Four parameters (flux, T, Q and targeting ratio) were used to evaluate permeability and targeting effect in skin.
The combined penetration modifiers played a general role on decreasing permeability without reducing skin retention. The most significant skin permeability decrement to MTZ was pig abdominal skin (permeability decrement was ∼20% for hairless mouse skin, 60% for pig abdominal skin and 40% for pig ear skin, respectively) while the strongest skin targeting effect appeared in hairless mouse skin (targeting ratios were 1.79 for hairless mouse skin, 1.24 for pig abdominal skin and 1.05 for pig ear skin, respectively) under the role of penetration modifiers.
Thickness of stratum corneum (SC) was the major factor impact on skin targeting effect. Selection criteria of skin models also have been discussed in this study.
本研究旨在探讨1,2 -己二醇（或1,2 -庚二醇）与1,4 -环己二醇的联合渗透促进剂在不同皮肤模型中对甲硝唑（MTZ）经皮吸收的局部皮肤靶向作用及机制。
将六种制剂分别应用于猪腹部皮肤和猪耳皮肤模型，并将结果与本实验室之前在无毛小鼠皮肤上得出的数据进行比较。使用四个参数（通量、T、Q和靶向率）来评估皮肤中的渗透性和靶向作用。
联合渗透促进剂在不降低皮肤滞留率的情况下，普遍起到降低渗透性的作用。对MTZ而言，皮肤渗透性降低最显著的是猪腹部皮肤（无毛小鼠皮肤的渗透性降低约20%，猪腹部皮肤为60%，猪耳皮肤为40%），而在渗透促进剂作用下，最强的皮肤靶向作用出现在无毛小鼠皮肤中（无毛小鼠皮肤的靶向率为1.79，猪腹部皮肤为1.24，猪耳皮肤为1.05）。
角质层（SC）厚度是影响皮肤靶向作用的主要因素。本研究还讨论了皮肤模型的选择标准。
