En tredimensionell in vitro modell av magtarmkanalen för att möjliggöra rationell utveckling av oralt administrerade läkemedel

Tidsperiod: 2019-01-01 till 2022-12-31

Projektledare: Christel Bergström

Medarbetare: Hélder Santos, Maria Karlgren

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 2 741 500 SEK

The vast majority of modern pharmacologically active compounds demands advanced drug delivery systems (ADDSs) to be developed as orally administered medicines. The goal for this project is to design lab bench models of the gut that can assess performance of ADDSs. A small intestinal-like absorption membrane will be designed by cell engineering with focus on incorporating transport proteins of importance for absorption of drugs. These cells will be explored for their potential to form small intestine-like tubes by making use of 3D printing and microfluidics. When the small intestine is established it will be coupled to similar models of the large intestine to allow regional differences, flow rates and transit times to inform on the performance of the ADDS. Finally, the system will be investigated for its potential use as disease models, herein exemplified with inflammatory bowel disease. All steps will be validated with drug-like molecules (small molecules) and biological drugs presented in ADDS of different types. When the objectives of the project are fulfilled, dynamic models for lab bench assessment of ADDS are designed where the interplay between release, dissolution, solubility, in vivo digestion and permeation is studied simultaneously. The models will provide insights into potential differences between patients, laying a platform for in vitro assessment of formulated personalized medicines such as dosage forms requiring local delivery to the colon.