Takeuchi Y, Yasukawa H, Yamaoka Y, Kato Y, Morimoto Y, Fukumori Y, Fukuda T
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Chem Pharm Bull (Tokyo). 1992 Jul;40(7):1887-92. doi: 10.1248/cpb.40.1887.
Fourier transform infrared/attenuated total reflection (FT-IR/ATR) spectroscopy was used to examine the effect of fatty acids, fatty amines and propylene glycol (PG) on the molecular mobility of rat stratum corneum lipids and keratinized proteins, using a hydrophobic solute, indomethacin, and a polar solute, 5- and 6-carboxyfluorescein (CF). Treatment of the skin with either oleic acid or oleylamine resulted in significant CH2 C-H asymmetric stretching band shifts and broadening. The extent of spectral alteration varied with the chemical structure of the penetrant. The penetrants increased the lipophilic indomethacin flux and shortened the lag times through the skin in vitro. The plot of frequency changes vs. indomethacin flux or lag time demonstrated a linear relationship, thus indicating that spectral alteration in CH2 C-H stretching regions of stratum corneum lipids may provide a reliable index for characterizing penetrants. The data also showed that the hydrophilic group which attached to the CH2 group in the penetrant molecules did not play a part in the membrane permeability enhancing action. Oleic acid and oleylamine appeared to induce a conformational alteration of the keratinized proteins from alpha-helix to beta sheet. Such alteration was also observed with PG treatment. Accumulation of CF was significantly increased by the PG pretreatment of the skin, thus suggesting that PG-induced protein conformational changes could be related to the enhancement of CF accumulation.
采用傅里叶变换红外/衰减全反射(FT-IR/ATR)光谱法,以疏水性溶质吲哚美辛和极性溶质5-羧基荧光素及6-羧基荧光素(CF)为指标,研究脂肪酸、脂肪胺和丙二醇(PG)对大鼠角质层脂质和角质化蛋白质分子流动性的影响。用油酸或油胺处理皮肤会导致显著的CH2 C-H不对称伸缩带位移和变宽。光谱改变的程度因渗透剂的化学结构而异。这些渗透剂增加了亲脂性吲哚美辛的通量,并缩短了其体外透过皮肤的滞后时间。频率变化与吲哚美辛通量或滞后时间的关系图呈线性关系,这表明角质层脂质CH2 C-H伸缩区域的光谱改变可为表征渗透剂提供可靠指标。数据还表明,渗透剂分子中与CH2基团相连的亲水基团在增强膜通透性的作用中不起作用。油酸和油胺似乎诱导了角质化蛋白质从α-螺旋构象转变为β-折叠构象。PG处理也观察到了这种改变。皮肤经PG预处理后CF的蓄积显著增加,这表明PG诱导的蛋白质构象变化可能与CF蓄积的增强有关。