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Capillary Bed Bioreactor: Improved Estimation Of Dermal Bioavailability

毛细管床生物反应器：改进皮肤生物利用度的估计

基本信息

批准号：
EP/M506850/1
负责人：
Marianne Ellis
金额：
$ 13.48万
依托单位：
University of Bath
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FM506850%2F1
关键词：
Capillary Bed Bioreactor Improved Estimation

项目摘要

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.

历史上，动物试验已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，包括评估化学品致敏潜力和效力的局部淋巴结试验（LLNA）。然而，近年来，人们一直在努力减少为支持新化妆品的风险评估而进行的动物试验水平，并朝着对人类暴露的机械理解的方向发展。因此，有必要开发用于预测新化学品的致敏潜力和/或效力的体外、化学或计算机模拟模型，以生成数据，从而增加体内情景预测的置信度。现在，人们已经很好地理解了导致人类皮肤过敏的化学和生物学事件，联合利华等公司利用这些信息在非动物模型中测试新化合物的安全性。将离体皮肤圆盘（来自整容手术）安装在扩散池中，并随时间监测供试品通过皮肤的渗透。虽然这已被证明是一个适当的模型，但它并不能真正代表活体皮肤。目前，很少有人知道通过真皮毛细血管的化学清除，这是一个缺口，我们的机械理解的生物利用度的局部应用的化学物质在皮肤过敏的启发。所提出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血管化床而更好地复制皮肤的体内环境及其血液供应。因此，它应该更准确地预测化学品通过皮肤的渗透，并提供更接近体内情况的数据。新的生物反应器在生理学上将比目前的模型更准确，因此可以潜在地改进我们皮肤致敏机制模型的输入，为我们提供更准确的不良结果预测。这反过来又会给我们更大的信心，使我们能够在未来对新成分进行风险评估，而无需进行动物试验。