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

本项目的目的是建立一个机制的理解渗透促进剂的作用，大分子药物分子的渗透性通过上皮经口给药。该项目通过开发机制理解和体外-计算机模拟-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，以期改善体外数据向体内（包括人体）的转化。低口服生物利用度的大分子药物，如肽，已指示其作为注射剂使用。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，该项目是这项研究工作的一部分。该项目符合EPSRC SFI CDT在预测药物科学和先进产品设计的变革性医疗保健技术主题。预测药物科学-该项目旨在建立渗透性增强剂的描述符与大分子药物渗透上皮的增强之间的关系。我们设想，在本项目结束时，我们将能够关联在体外，在硅片和在体内的渗透性增强的数据，作为渗透性增强剂选择的预测工具。先进的产品设计-该项目将导致先进的药物产品的设计的基础上渗透增强技术。项目对齐预测药物科学和先进的产品设计

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