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

本项目旨在建立对渗透促进剂在口服后大分子药物分子通过上皮细胞的渗透性中的作用的机制的理解。该项目通过发展机理理解和体外-体内-硅-体内关系作为预测工具来实现这一点，以优化渗透性增强技术的配方设计，以期改进体外数据到体内(包括人体)的转换。大分子药物，如多肽的口服生物利用度低，指导了它们作为注射剂的使用。需要新的解决方案来增加大分子药物在肠道上皮细胞中的转运，从而提高口服后的生物利用度。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在预测制药科学和高级产品设计的变革性医疗技术主题中保持一致。预测药学-该项目旨在建立通透性增强剂的描述参数与促进大分子药物通过上皮细胞之间的关系。我们预计，在这个项目结束时，我们将能够在体外、硅胶和活体数据中关联渗透性增强的数据，作为选择渗透性增强剂的预测工具。先进的产品设计-该项目将导致基于渗透性增强技术的先进制药产品的设计。该项目与预测制药科学和先进产品设计相结合

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