pH4HIF · Effect of pH on colloidal structures in human intestinal fluids and intestinal absorption of anticancer drugs
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2023-09-01 → 2025-08-31
- EU contribution
- €175,920
- Participants
- 2
- Scheme
- HORIZON-TMA-MSCA-PF-EF
Lines connect the coordinator with its partners.
Results in brief
Effect of pH on colloidal structures in human intestinal fluids and intestinal absorption of anticancer drugs
Improving oral drug delivery is crucial for ensuring safe and effective treatment. A major challenge in oral drug delivery is the significant variability in intestinal drug absorption. This variability is largely influenced by the complex and dynamic composition of human intestinal fluids (HIF), which differs among individuals and is affected by whether a person is in a fed or fasted state. HIF contains various components such as bile salts, cholesterol, proteins, phospholipids, and lipids, and its pH can vary widely. These factors play a key role in how well a drug dissolves and is absorbed in the intestine. Understanding the mechanisms of drug absorption is particularly important, as changes in pH and food intake can lead to drug under- or overdose. One promising approach to better understand intestinal drug absorption is to investigate the pH effect. pH can influence drug absorption in two main ways. The first is a direct effect, where pH changes the ionization of the drug, which is a well-known mechanism. The second is an indirect effect, where pH alters the colloidal structures in HIF, also impacting drug absorption. Although the indirect pH effect is much less understood, it may play a significant role in affecting drug solubility and absorption. The overall objective of this project was to investigate the pH effect on the colloidal structures of HIF in the fed state and its impact on drug solubility.
Data: CORDIS, © European Union
Project objective
Oral administration followed by intestinal absorption is the preferred way to deliver drugs to the body. Therefore, estimating thecorrect oral dose to achieve a therapeutic effect is an important challenge when developing drug products. Predicting intestinal drugabsorption needs to consider multiple influencing factors, including properties of the drug, the formulation, and the human intestinalfluids (HIF). One of the critical factors of HIF is pH, as it may influence intestinal drug absorption both directly and indirectly. The directeffect of pH on a drugs ionisation state and, subsequently, intestinal absorption is widely known. However, the effect of pH on thesolubilisation and absorption of lipophilic drugs by changing the colloidal structures present in HIF, has not yet been systematicallyanalysed.Understanding this indirect pH effect is especially needed to improve dose predictions for drugs with a narrow therapeutic windowsuch as anticancer drugs, and address both inefficiency and potential side effects. The proposed project therefore aims to understandand predict the pH effect on colloidal structures in HIF and how it affects the absorption potential of anticancer drugs in both fastedand 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 invivo methods with the applicants experience in predictive in silico modelling. This approach will provide unique insights into theindirect pH effect on drug absorption and contribute to the development of in silico predictive models to guide the early-stageformulation and dose optimisation of anticancer drugs. As such, the project will have important value for pipelining new anticancerdrugs and will benefit the European Commission priorities for 2019-2024, such as the pharmaceutical strategy and Europes BeatingCancer Plan.
Original text from CORDIS.
Participants
Links
- View on CORDIS
- DOI: 10.3030/101108993
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e509530217&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e520560058&appId=PPGMS
Data: CORDIS, © European Union