Lu Guang Wei, Valiveti Satyanarayana, Spence Julie, Zhuang Christine, Robosky Lora, Wade Kimberly, Love Ann, Hu Lain-Yen, Pole David, Mollan Matt
Pfizer Global Research and Development, Ann Arbor, MI 48105, USA.
Int J Pharm. 2009 Feb 9;367(1-2):37-43. doi: 10.1016/j.ijpharm.2008.09.025. Epub 2008 Sep 24.
To understand drug delivery to the sebum filled hair and sebaceous follicles, it is essential to use an artificial sebum as a surrogate of the human sebum for the investigation of drug transport properties. Artificial sebum L was developed in-house based on the chemical similarity to human sebum. The partition and diffusion of model compounds (ethyl 4-hydroxybenzoate, butyl 4-hydroxybenzoate, and hexyl 4-hydroxybenzoate) were measured in human sebum, hamster ear and body sebum (a commonly used animal model), and four representative artificial sebum samples (N, S, F, and L) in which artificial sebums, N, S and F were selected based on the available literature. DSC and NMR studies were also conducted on all sebums to compare their melting properties and chemical compositions. In vitro studies show that the partition coefficients of the three model compounds in artificial sebum L were similar to that of human sebum, whereas the hamster ear and body sebum, and other three artificial sebum samples were different from that of human sebum. Additionally, the in vitro sebum flux (microg/(cm(2)min) of three model compounds through artificial sebum L was closer to that of human sebum when compared with the other three artificial sebum (N, S and F), hamster body and hamster ear sebum. The results of this study indicate that the artificial sebum L could be used as an alternative to human sebum, as the physicochemical properties of this artificial sebum is relatively similar to human sebum.
为了解药物向充满皮脂的毛发和皮脂腺毛囊的递送情况,使用人工皮脂作为人皮脂的替代物来研究药物转运特性至关重要。人工皮脂L是根据与人皮脂的化学相似性在内部开发的。在人皮脂、仓鼠耳部和身体皮脂(一种常用的动物模型)以及四种代表性的人工皮脂样品(N、S、F和L)中测量了模型化合物(4-羟基苯甲酸乙酯、4-羟基苯甲酸丁酯和4-羟基苯甲酸己酯)的分配和扩散情况,其中人工皮脂N、S和F是根据现有文献选择的。还对所有皮脂进行了差示扫描量热法(DSC)和核磁共振(NMR)研究,以比较它们的熔化特性和化学组成。体外研究表明,三种模型化合物在人工皮脂L中的分配系数与人皮脂相似,而仓鼠耳部和身体皮脂以及其他三种人工皮脂样品与人皮脂不同。此外,与其他三种人工皮脂(N、S和F)、仓鼠身体和仓鼠耳部皮脂相比,三种模型化合物通过人工皮脂L的体外皮脂通量(μg/(cm²·min))与人皮脂更接近。这项研究的结果表明,人工皮脂L可作为人皮脂的替代品,因为这种人工皮脂的物理化学性质与人皮脂相对相似。