Capillary Bed Bioreactor: Improved Estimation Of Dermal Bioavailability

从历史上看，动物试验被用于支持与化妆品成分相关的各种毒理学终点的风险评估，包括局部淋巴结法(LLNA)，以评估阿昔洛韦的致敏潜力和效力。然而，近年来，一直在推动降低动物试验水平，以支持新化妆品的风险评估，并朝着对人类暴露的机械性理解的方向发展。因此，在体外、化学或计算机模型中发展机制/生物学相关的预测新化学品的敏化潜力和/或效力是必要的，以产生数据，从而增加对体内情景预测的信心。人们现在已经很好地了解了导致人类皮肤敏感化的化学和生物事件，联合利华等公司在非动物模型中使用这些信息来测试新化合物的安全性。体外皮肤的圆盘(来自整容手术)被安装在扩散池中，并随着时间的推移监测测试物品通过皮肤的渗透情况。虽然这被证明是一个合适的模型，但它并不能真正代表活生生的皮肤。目前，关于通过皮肤毛细血管清除化学物质的情况知之甚少，这是我们对局部应用的化学物质在诱发皮肤敏化过程中的生物利用度的机械理解上的一个空白。拟议的毛细管床生物反应器(CBB)通过以中空纤维膜的形式提供假性血管床，更好地复制了皮肤及其血液供应的体内环境。因此，它应该更准确地预测化学物质通过皮肤的渗透，并提供更接近InVivo情景的数据。新的生物反应器将比目前的模型在生理上更准确，因此可以潜在地改进我们的皮肤敏化机制模型的输入，为我们提供更准确的逆境结果预测。这反过来将给我们更大的信心，使我们有能力在未来评估新成分的风险，而不需要进行动物试验。

Historically, animal testing has been used to support risk assessment for a variety of toxicological endpoints related tocosmetic ingredients, including the local lymph node assay (LLNA) to assess the sensitization potential and potency of achemical. However, in recent years, there has been a continuous drive to reduce the level of animal testing undertaken tosupport risk assessments for new cosmetic products, and a move towards a mechanistic understanding of humanexposure. Consequently, the development of mechanistic/biologically relevant in vitro, in chemico or in silico models forpredicting the sensitising potential and/or potency of new chemicals is necessary to generate data leading to increasedconfidence in predictions of in vivo scenarios. The chemical and biological events driving the induction of human skinsensitisation are now well understood and companies such as Unilever use this information in non-animal models to testthe safety of new compounds. Discs of ex vivo skin (from cosmetic surgery procedures) are mounted in diffusion cells andthe permeation of a test item through the skin is monitored over time. While this has proved to be an adequate model, itdoes not truly represent living skin. At present, little is known regarding chemical clearance via dermal capillaries, and thisis a gap in our mechanistic understanding of the bioavailability of a topically applied chemical in the elicitation of skinsensitisation. The proposed capillary bed bioreactor (CBB) better replicates the in vivo environment of the skin and itsblood supply by providing a bed of pseudovascularisation in the form of hollow fibre membranes. Therefore it should moreaccurately predict permeation of chemicals through the skin, and provide data that more closely resembles that of the invivo scenario. The new bioreactor will be more physiologically accurate than the current model and can thereforepotentially refine inputs to our mechanistic models for skin sensitisation, to give us more accurate predictions of adverseoutcomes. This in turn will give greater confidence in our ability to risk assess new ingredients in the future without therequirement for animal testing.