Tanojo H, Bouwstra J A, Junginger H E, Boddé H E
Division of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, The Netherlands.
Pharm Res. 1997 Jan;14(1):42-9. doi: 10.1023/a:1012099216060.
This study aims to elucidate the skin permeation enhancement and the skin perturbation effects of a number of fatty acids, i.e. straight-chain saturated (SFA), monounsaturated (MUFA) and polyunsaturated acids (PUFA).
The skin permeation enhancement effects were studied using human stratum comeum (SC) and p-aminobenzoic acid (PABA) as a model permeant. The fatty acids in propylene glycol (FA/PG) were applied according to a pre-treatment/co-treatment protocol. The perturbation effects were studied using differential thermal analysis (DTA) on SC after pretreatment with FA/PG.
SFA with 6 to 12 carbons exhibit a parabolic correlation between enhancement effect and chain-length, with a maximum at nonanoic-decanoic acids (with 9 and 10 carbons). Nonanoic and decanoic acids exert barely noticeable effects on the thermal behaviour of SC, suggesting that they easily mix with the skin lipids. All cis-6-, 9-, 11- or 13-octadecenoic acids (MUFA) enhance the permeation of PABA to the same extent. DTA revealed that the cis-9- and 13-isomers form a separate domain containing mostly the pure fatty acids within the SC lipids and suppress the lipid transitions at 70 degrees/80 degrees C. PUFA--linoleic (LA), alpha-linolenic (ALA) and arachidonic acids--enhance PABA permeation stronger than MUFA but additional double bonds do not further increase the degree of enhancement. LA and ALA form separate domains but do not completely suppress the SC lipid transitions at 70 degrees/80 degrees C. Increase in the enthalpy changes of 70 degrees/80 degrees transitions linearly correlates to the decrease in the permeability coefficients, suggesting that an increased perturbation of the skin lipids not necessarily has to yield an increased PABA permeation.
The enhancement effects of fatty acids on the PABA penetration through SC are structure-dependent, associated with the existence of a balance between the permeability of pure fatty acids across SC and the interaction of the acids to skin lipids.
本研究旨在阐明多种脂肪酸，即直链饱和脂肪酸（SFA）、单不饱和脂肪酸（MUFA）和多不饱和脂肪酸（PUFA）对皮肤渗透的增强作用以及对皮肤的扰动效应。
以人角质层（SC）和对氨基苯甲酸（PABA）作为模型渗透物，研究脂肪酸对皮肤渗透的增强作用。按照预处理/共处理方案，将脂肪酸添加到丙二醇（FA/PG）中使用。在用FA/PG预处理后的SC上，采用差示热分析（DTA）研究扰动效应。
含有6至12个碳原子的SFA在增强效果与链长之间呈现抛物线相关性，在壬酸和癸酸（含9和10个碳原子）时达到最大值。壬酸和癸酸对SC的热行为几乎没有显著影响，表明它们易于与皮肤脂质混合。所有顺式-6-、9-、11-或13-十八碳烯酸（MUFA）对PABA渗透的增强程度相同。DTA显示，顺式-9-和13-异构体在SC脂质中形成一个主要包含纯脂肪酸的单独区域，并抑制70℃/80℃时的脂质转变。PUFA——亚油酸（LA）、α-亚麻酸（ALA）和花生四烯酸——比MUFA更能增强PABA的渗透，但额外的双键不会进一步增加增强程度。LA和ALA形成单独区域，但不会完全抑制70℃/80℃时SC脂质的转变。70℃/80℃转变的焓变增加与渗透系数的降低呈线性相关，这表明皮肤脂质扰动增加不一定会导致PABA渗透增加。
脂肪酸对PABA透过SC的增强作用取决于结构，与纯脂肪酸透过SC的渗透性和酸与皮肤脂质的相互作用之间的平衡有关。
