Oral delivery of macromolecular drug - a mechanistic study of the mode of action of permeation enhancers for increasing drug bioavailability

大分子药物的口服给药——渗透促进剂提高药物生物利用度作用模式的机制研究

• 批准号: 2283829
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2283829
• 关键词: Oral; delivery; macromolecular; drug; mechanistic

This project aims to build a mechanistic understanding of the role of permeation enhancers in permeability of macromolecular drug molecules across epithelium following oral administration. The project approaches this via developing mechanistic understanding and in vitro - in silico - in vivo relationship as a prediction tool to optimise formulation design of permeability enhancement technology, with the view to improving the translation of in vitro data into in vivo (including human). Low oral bioavailability of macromolecular drugs, such as peptides, has directed their use as injections. New solutions are needed to increase transport of macromolecular drugs across intestinal epithelium and consequently improve their bioavailability following oral administration. AstraZeneca is developing a permeability enhancer technology to increase oral bioavailability of macromolecular drugs, and this project is a part of this research effort.The project aligns with the EPSRC SFI CDT in Transformative Healthcare Technologies themes of Predictive Pharmaceutical Sciences and Advanced Product Design. Predictive Pharmaceutical Sciences - the project aims to establish a relationship between the descriptors of permeability enhancer and enhancement in macromolecular drug permeation across epithelium. We envisage that at the end of this project we will be able to correlate in vitro, in silico and in vivo data on permeability enhancement, as a predictive tool for permeability enhancer selection. Advanced Product Design - the project will lead to a design of advanced pharmaceutical products based on permeability enhancement technology.Project aligned to Predictive Pharmaceutical Sciences and Advanced Product Design

该项目旨在从机制上理解渗透促进剂在口服给药后大分子药物分子穿过上皮细胞的渗透性中的作用。该项目通过发展机制理解和体外-计算机-体内关系作为预测工具来实现这一目标，以优化渗透性增强技术的配方设计，以期改善体外数据到体内（包括人类）的转化。大分子药物（例如肽）的口服生物利用度较低，因此将其用作注射剂。需要新的解决方案来增加大分子药物穿过肠上皮的转运，从而提高口服给药后的生物利用度。阿斯利康正在开发一种渗透性增强剂技术，以提高大分子药物的口服生物利用度，该项目是该研究工作的一部分。该项目与 EPSRC SFI CDT 的预测制药科学和先进产品设计的变革性医疗技术主题相一致。预测药物科学 - 该项目旨在建立渗透性增强剂描述符与大分子药物跨上皮渗透增强之间的关系。我们设想，在该项目结束时，我们将能够将通透性增强的体外、计算机和体内数据关联起来，作为通透性增强剂选择的预测工具。先进产品设计 - 该项目将基于渗透性增强技术设计先进的药品。项目与预测制药科学和先进产品设计相结合