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Effect of pH on colloidal structures in human intestinal fluids and intestinal absorption of anticancer drugs

Objective

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 drugs 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 applicants 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 Europes Beating
Cancer Plan.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

See all projects funded under this funding scheme

Call for proposal

(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

KATHOLIEKE UNIVERSITEIT LEUVEN
Net EU contribution
€ 175 920,00
Address
OUDE MARKT 13
3000 Leuven
Belgium
Region
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Partners (1)