This project researches the effect of pH on colloidal structures in human intestinal fluids and intestinal absorption of anticancer drugs. It will have important value for pipelining new anticancer drugs and will benefit the European Commission priorities for 2019-2024, such as the pharmaceutical strategy and Europe’s Beating Cancer Plan. 

Project description

Oral administration followed by intestinal absorption is the preferred way to deliver drugs to the body. Therefore, estimating the correct oral dose to achieve a therapeutic effect is an important challenge when developing drug products. Predicting intestinal drug absorption needs to consider multiple influencing factors, including properties of the drug, the formulation, and the human intestinal fluids (HIF). One of the critical factors of HIF is pH, as it may influence intestinal drug absorption both directly and indirectly. The direct effect of pH on a drug’s ionisation state and, subsequently, intestinal absorption is widely known. However, the effect of pH on the solubilisation and absorption of lipophilic drugs by changing the colloidal structures present in HIF, has not yet been systematically analysed. Understanding this indirect pH effect is especially needed to improve dose predictions for drugs with a narrow therapeutic window such as anticancer drugs, and address both inefficiency and potential side effects.

The proposed project therefore aims to understand and predict the pH effect on colloidal structures in HIF and how it affects the absorption potential of anticancer drugs in both fasted and fed state conditions. To achieve its goal, the project combines the expertise of the host group at KU Leuven in absorption profiling using in vitro and in vivo methods with the applicant’s experience in predictive in silico modelling. This approach will provide unique insights into the indirect pH effect on drug absorption and contribute to the development of in silico predictive models to guide the early-stage formulation and dose optimisation of anticancer drugs. As such, the project will have important value for pipelining new anticancer drugs and will benefit the European Commission priorities for 2019-2024, such as the pharmaceutical strategy and Europe’s Beating Cancer Plan.