Nair Vinod B, Panchagnula Ramesh
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S Nagar, Punjab, 160 062, India.
Pharmacol Res. 2003 Jun;47(6):563-9. doi: 10.1016/s1043-6618(03)00016-1.
The aim of this study was to assess the effects of fatty acids and iontophoretic mode of penetration enhancement on transdermal delivery of Arginine Vasopressin (AVP). Sprague-Dawley (SD) rat skin was pretreated with fatty acids (e.g. 5% w/v, lauric acid, oleic acid, and linoleic acid in ethanol:water (EtOH:W, 2:1 system) for 2h and iontophoresis in vitro, separately or together. The results indicate that all fatty acids studied increased (P<0.05) the flux of AVP in comparison to control (not pretreated with enhancer) and their effectiveness in flux enhancement was comparable. Further, oleic acid in combination with iontophoresis significantly increased the permeation of AVP both in comparison to pretreatment with fatty acids and iontophoresis alone. However, iontophoresis did not further increase the permeation of AVP through linoleic acid pretreated skin. Fourier transform infrared (FT-IR) spectroscopic studies revealed that EtOH:W (2:1) system is not effective in lipid extraction. The shift to higher wavenumbers of the symmetric and asymmetric stretching peaks at 2850 and 2920cm(-1) revealed that at the concentration used, oleic acid and linoleic acid caused fluidization of stratum corneum (SC) lipids. This study provides direct evidence that oleic acid in EtOH:W (2:1) system causes disruption of the SC lipid lamellae and that a combination of oleic acid with iontophoresis further enhances the effects of oleic acid in a synergistic manner.
本研究的目的是评估脂肪酸和离子导入增强渗透模式对精氨酸加压素(AVP)经皮给药的影响。将Sprague-Dawley(SD)大鼠皮肤分别或一起用脂肪酸(例如在乙醇:水(EtOH:W,2:1体系)中的5%w/v月桂酸、油酸和亚油酸)预处理2小时并进行体外离子导入。结果表明,与对照(未用增强剂预处理)相比,所有研究的脂肪酸均增加了(P<0.05)AVP的通量,并且它们在通量增强方面的有效性相当。此外,与单独用脂肪酸预处理和离子导入相比,油酸与离子导入联合使用显著增加了AVP的渗透。然而,离子导入并未进一步增加AVP通过亚油酸预处理皮肤的渗透。傅里叶变换红外(FT-IR)光谱研究表明,EtOH:W(2:1)体系在脂质提取方面无效。在2850和2920cm(-1)处对称和不对称拉伸峰向更高波数的移动表明,在所使用的浓度下,油酸和亚油酸导致角质层(SC)脂质流化。本研究提供了直接证据,即EtOH:W(2:1)体系中的油酸会破坏SC脂质片层,并且油酸与离子导入的组合以协同方式进一步增强了油酸的作用。