Faculty of Pharmacy, Department of Pharmaceutics, Hamdard University, M. B. Road, New Delhi, India.
Drug Dev Ind Pharm. 2011 May;37(5):583-96. doi: 10.3109/03639045.2010.532219.
The greatest obstacle for transdermal delivery is the barrier property of the stratum corneum. Many approaches have been employed to breach the skin barrier; the most widely used one is that of chemical penetration enhancers. Of the penetration enhancers, terpenes are arguably the most highly advanced and proven category.
The aim of this investigation was to study effectiveness and mechanism of seven novel terpenes, namely iso-eucalyptol, β-citronellene, valencene, rose oxide, safranal, lavandulol acetate, and prenol, as potential penetration enhancers for improved skin permeation of valsartan through rat skin and human cadaver skin (HCS) with reference to established terpene eucalyptol.
Skin permeation studies were carried out using Automated Transdermal Diffusion Cell Sampling System (SFDC 6, LOGAN Instruments Corp., NJ) on rat skin and HCS. The mechanism of skin permeation enhancement of valsartan by terpenes treatment was evaluated by Fourier transform infrared spectroscopy (FT-IR) analysis, differential scanning calorimetry (DSC) thermogram, and histopathological examination.
Among all study enhancers, iso-eucalyptol produced the maximum enhancement via rat skin [enhancement ratio (ER) = 7.4] and HCS (ER = 3.60) over control. FT-IR spectra and DSC thermogram of skin treated with aforesaid terpenes indicated that permeation occurred due to the disruption of lipid bilayers. No apparent skin irritation (erythema, edema) was observed on treatment with terpenes except β-citronellene, safranal, lavandulol acetate, and prenol, which caused mild irritation.
It is concluded that the iso-eucalyptol can be successfully used as safe and potential penetration enhancer for enhancement of skin permeation of lipophilic drug such as valsartan.
经皮递送的最大障碍是角质层的屏障特性。人们已经采用了许多方法来突破皮肤屏障；最广泛使用的方法是使用化学渗透增强剂。在渗透增强剂中，萜类化合物可以说是最先进和最成熟的一类。
本研究旨在研究七种新型萜类化合物（异桉叶油醇、β-香茅烯、缬烯、氧化玫瑰、藏红花醛、乙酸薰衣草醇和烯丙醇）作为潜在的渗透增强剂，以提高缬沙坦通过大鼠皮肤和人体尸体皮肤（HCS）的皮肤渗透效果，并参考已建立的萜类化合物桉叶油醇。
使用自动化经皮扩散细胞采样系统（SFDC 6，LOGAN Instruments Corp.，NJ）在大鼠皮肤和 HCS 上进行皮肤渗透研究。通过傅里叶变换红外光谱（FT-IR）分析、差示扫描量热法（DSC）图谱和组织病理学检查评估萜类化合物处理对缬沙坦皮肤渗透增强的机制。
在所有研究的增强剂中，异桉叶油醇通过大鼠皮肤[增强比（ER）= 7.4]和 HCS（ER= 3.60）产生了最大的增强作用。经上述萜类化合物处理的皮肤的 FT-IR 光谱和 DSC 图谱表明，渗透是由于脂质双层的破坏而发生的。除了β-香茅烯、藏红花醛、乙酸薰衣草醇和烯丙醇外，用萜类化合物处理皮肤时没有观察到明显的皮肤刺激（红斑、水肿），它们会引起轻微的刺激。
可以得出结论，异桉叶油醇可以成功用作安全且有潜力的渗透增强剂，以增强亲脂性药物（如缬沙坦）的皮肤渗透。
