Madsen Jakob Torp, Vogel Stefan, Johansen Jeanne Duus, Sørensen Jens Ahm, Andersen Klaus Ejner, Nielsen Jesper Bo
Department of Dermatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
Cutan Ocul Toxicol. 2011 Mar;30(1):38-44. doi: 10.3109/15569527.2010.521220. Epub 2010 Nov 23.
Formulation of the contact allergens dinitrochlorobenzene and isoeugenol in ethanolic liposomes (ethosomes) increases their sensitizing properties in the local lymph node assay compared with an ethanol-water formulation of the allergens. Likewise, isoeugenol and methyldibromo-glutaronitrile formulated in ethosomes enhanced the patch test reactions in sensitized human volunteers. The relationship between the percutaneous penetration/absorption and sensitization/elicitation phases of contact allergy is not well elucidated.
The aim of this study was to investigate whether the observed increased sensitizing and elicitation properties following the formulation of selected contact allergens in ethosomes could be explained by a change in release kinetics of the allergens and their pattern of percutaneous penetration and absorption as well as allergen deposition in epidermis and dermis.
Release kinetics were studied using dialysis bags, and samples were taken at selected time points until equilibrium was reached. Percutaneous absorption and penetration were studied using human skin on Franz cells, and receptor fluid samples were taken at selected time points. Experiments were terminated after 24 hours, and deposition of allergen in epidermis and dermis was measured. Maximum flux and lag time were calculated.
Ethosome formulation decreased the release of both allergens compared with the ethanol-water formulation. Ethosome formulation of dinitrochlorobenzene increased its percutaneous penetration but reduced the percutaneous penetration of isoeugenol compared with control formulations. Likewise, all other calculated parameters showed an opposite trend for the 2 allergens in ethosomes and ethanol-water.
The present study demonstrates that identical ethosomes affect the percutaneous penetration characteristics of 2 allergens differently. Thus, our results indicate that each combination of an allergen and a vehicle needs to be evaluated separately. The exact mechanistic relationship between percutaneous penetration, release kinetics, and allergenicity of chemicals in various vehicles remains to be clarified.
与过敏原的乙醇 - 水制剂相比，将接触性过敏原二硝基氯苯和异丁香酚制成乙醇脂质体（醇质体）后，在局部淋巴结试验中其致敏特性增强。同样，制成醇质体的异丁香酚和甲基二溴戊二腈在致敏的人类志愿者中增强了斑贴试验反应。接触性过敏的经皮渗透/吸收与致敏/激发阶段之间的关系尚未得到充分阐明。
本研究的目的是调查将选定的接触性过敏原制成醇质体后观察到的致敏和激发特性增加，是否可以通过过敏原释放动力学的变化、其经皮渗透和吸收模式以及过敏原在表皮和真皮中的沉积来解释。
使用透析袋研究释放动力学，并在选定的时间点取样，直至达到平衡。使用Franz扩散池上的人体皮肤研究经皮吸收和渗透，并在选定的时间点采集受体液样本。24小时后终止实验，并测量过敏原在表皮和真皮中的沉积。计算最大通量和滞后时间。
与乙醇 - 水制剂相比，醇质体制剂降低了两种过敏原的释放。与对照制剂相比，二硝基氯苯的醇质体制剂增加了其经皮渗透，但降低了异丁香酚的经皮渗透。同样，对于醇质体和乙醇 - 水制剂中的两种过敏原，所有其他计算参数均显示出相反的趋势。
本研究表明相同的醇质体对两种过敏原的经皮渗透特性影响不同。因此，我们的结果表明，每种过敏原与载体的组合都需要单独评估。各种载体中化学物质的经皮渗透、释放动力学和致敏性之间的确切机制关系仍有待阐明。
