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

点击翻译按钮获取中文摘要

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