Llewelyn Victoria K, Berger Lee, Glass Beverley D
Pharmacy, College of Medicine and Dentistry, James Cook University, Townsville, 4811, Australia.
One Health Research Group, Melbourne Veterinary School, University of Melbourne, Werribee, 3029, Australia.
Heliyon. 2019 Aug 16;5(8):e02127. doi: 10.1016/j.heliyon.2019.e02127. eCollection 2019 Aug.
Rarely do commercial chemical products contain solely the active chemical/ingredient. It is therefore important to consider whether ingredients other than the active may: 1) alter absorption of the active chemical, or 2) be absorbed themselves, resulting in systemic effects. Frogs have highly permeable skin and are routinely exposed to commercial chemical products in the environment or therapeutically. Ethanol and propylene glycol (PG), which have known penetration-enhancing effects, are commonly included in such products. The current study has therefore investigated the absorption kinetics through skin of three model chemicals - caffeine, benzoic acid, and ibuprofen - formulated individually as solutions containing: 1%, 10% or 30% v/v ethanol, or 20% v/v PG. Differential scanning calorimetry and histology were used to characterise fresh frog skin, investigate the mechanism of these enhancers in frog skin, and to determine whether these enhancers significantly affected skin structure. Results showed that the extent of absorption enhancement was influenced by chemical, enhancer and skin region, and that enhancement was generally not consistent for individual enhancers or skin regions. The exception was 1% v/v ethanol, which did not significantly alter flux across the skin for any of the chemicals evaluated. Caffeine absorption was not enhanced by any of the investigated penetration enhancers, and was in fact significantly reduced by 30% v/v ethanol and PG. Ethanol caused concentration-dependant changes in skin morphology and should be avoided in concentrations ≥10% v/v. PG, however, caused minimal changes to the skin and consistently improved absorption of benzoic acid and ibuprofen through all skin regions. Owing to the significant changes in skin structure following ≥10% v/v ethanol exposure, it is recommended to avoid its use in frogs. For enhancement of penetration of moderately-to-highly lipophilic chemicals, this study has identified 20% v/v PG should to be the enhancer of choice.
市售化学产品很少仅含有活性化学物质/成分。因此，考虑活性成分以外的其他成分是否会：1）改变活性化学物质的吸收，或2）自身被吸收并产生全身效应，这一点很重要。青蛙的皮肤具有高度渗透性，经常在环境中或治疗过程中接触市售化学产品。已知具有渗透增强作用的乙醇和丙二醇（PG）通常包含在这类产品中。因此，本研究调查了三种模型化学品——咖啡因、苯甲酸和布洛芬——分别配制成含有1%、10%或30%（v/v）乙醇或20%（v/v）PG的溶液后通过皮肤的吸收动力学。采用差示扫描量热法和组织学来表征新鲜青蛙皮肤，研究这些增强剂在青蛙皮肤中的作用机制，并确定这些增强剂是否会显著影响皮肤结构。结果表明，吸收增强程度受化学物质、增强剂和皮肤区域的影响，而且对于单个增强剂或皮肤区域而言，增强效果通常并不一致。例外的是1%（v/v）乙醇，对于所评估的任何化学物质，它都不会显著改变经皮通量。所研究的任何渗透增强剂都不会增强咖啡因的吸收，事实上，30%（v/v）乙醇和PG会使其吸收显著降低。乙醇会引起皮肤形态的浓度依赖性变化，浓度≥10%（v/v）时应避免使用。然而，PG对皮肤的影响极小，并且能持续改善苯甲酸和布洛芬在所有皮肤区域的吸收。由于暴露于≥10%（v/v）乙醇后皮肤结构会发生显著变化，建议避免在青蛙身上使用。对于增强中度至高度亲脂性化学物质的渗透，本研究已确定20%（v/v）PG应为首选增强剂。
