离子电渗疗法与一系列脂肪酸对促黄体激素释放激素透过猪皮肤的协同作用。

Synergistic effect of iontophoresis and a series of fatty acids on LHRH permeability through porcine skin.

作者信息

Bhatia K S, Singh J

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105, USA.

出版信息

J Pharm Sci. 1998 Apr;87(4):462-9. doi: 10.1021/js970301f.

DOI:10.1021/js970301f

PMID:9548900

Abstract

The effect of chemical penetration enhancers (e.g., fatty acids) in combination with iontophoresis was examined on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through porcine skin. Porcine epidermis was pretreated with either ethanol (EtOH) or 10% fatty acid/EtOH. The permeability coefficient of LHRH was significantly (p < 0.05) greater through EtOH, lauric acid/EtOH, palmitic acid/EtOH, oleic acid/EtOH, linoleic acid/EtOH, and linolenic acid/EtOH treated epidermis than the control (untreated epidermis). Iontophoresis further enhanced the permeability of LHRH (p < 0.05) through enhancer-pretreated epidermis in comparison with corresponding passive permeability. Among saturated fatty acids tested, 10% palmitic acid/iontophoresis showed the highest permeability coefficient [(59.52 +/- 2.40) x 10(-4) cm/h], which was approximately 16-fold higher than that of the control [(3.57 +/- 0.41) x 10(-4) cm/h]. Unsaturated cis-octadecenoic acids were more effective penetration enhancers when compared with octadecanoic acid. Among cis-octadecenoic acids in combination with EtOH, the greater iontophoretic permeability coefficient [(59.18 +/- 12.43) x 10(-4) cm/h] was obtained through linolenic acid treated epidermis, which was significantly greater (p < 0.05) than through saturated octadecanoic acid treated epidermis [(29.08 +/- 3.18) x 10(-4) cm/h]. Also, pretreatment of epidermis with 5% linolenic acid/propylene glycol (PG) resulted in greater (p < 0.05) iontophoretic flux of LHRH in comparison to 5% linolenic acid/EtOH. Furthermore, increases in the degree of unsaturation in octadecenoic acids did not produce corresponding increases in the degree of enhancement. Reversibility studies revealed that the postrecovery passive flux of LHRH through 5% linolenic acid in combination with EtOH or PG/iontophoresis treated epidermis was significantly (p < 0.05) reduced than the prerecovery value but could not completely recover to the baseline flux (i.e., flux of LHRH through untreated epidermis).

摘要

研究了化学渗透促进剂（如脂肪酸）与离子电渗疗法联合使用对猪皮肤中促黄体生成激素释放激素（LHRH）体外渗透性的影响。猪表皮用乙醇（EtOH）或10%脂肪酸/EtOH预处理。LHRH通过乙醇、月桂酸/EtOH、棕榈酸/EtOH、油酸/EtOH、亚油酸/EtOH和亚麻酸/EtOH处理的表皮的渗透系数显著高于对照组（未处理的表皮）（p<0.05）。与相应的被动渗透性相比，离子电渗疗法进一步提高了LHRH通过渗透促进剂预处理表皮的渗透性（p<0.05）。在所测试的饱和脂肪酸中，10%棕榈酸/离子电渗疗法显示出最高的渗透系数[（59.52±2.40）×10⁻⁴cm/h]，约为对照组[（3.57±0.41）×10⁻⁴cm/h]的16倍。与十八烷酸相比，不饱和顺式十八碳烯酸是更有效的渗透促进剂。在与EtOH联合使用的顺式十八碳烯酸中，通过亚麻酸处理的表皮获得了更大的离子电渗渗透系数[（59.18±12.43）×10⁻⁴cm/h]，显著高于通过饱和十八烷酸处理的表皮[（29.08±3.18）×10⁻⁴cm/h]（p<0.05）。此外，用5%亚麻酸/丙二醇（PG）预处理表皮与5%亚麻酸/EtOH相比，LHRH的离子电渗通量更大（p<0.05）。此外，十八碳烯酸不饱和度的增加并未导致相应的增强程度增加。可逆性研究表明，LHRH通过5%亚麻酸与EtOH或PG/离子电渗疗法处理的表皮的恢复后被动通量显著低于恢复前的值（p<0.05），但不能完全恢复到基线通量（即LHRH通过未处理表皮的通量）。