3D-Printing of Permeation Membranes for Biorelevant Permeation Studies in an Artificial Model of the Small Intestine

• Applicant: Dr. Julian Quodbach
• Subject Area: Pharmacy
• Term: from 2018 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 416044197

Dosage forms are usually administered orally, as this is the simplest and most uncomplicated delivery route. A disadvantage of oral administration is that the drug substance has to dissolve from the dosage form before it can be absorbed via the mucosa of the (small) intestine. If the drug is not absorbed, no effect can be expected. Several in vitro models have been proposed and developed for permeation studies. They are based either on cell-based membranes or on purely artificial membranes. An advantage of cell-based assays is that drug transport across the cell membrane via transport proteins is reflected. However, the costly and labor intensive cell cultivation led to the development of artificial, lipid-based membranes that are easy and cheap to manufacture and are therefore more suitable for routine testing. They cannot reflect active transport via transport proteins as they are naturally not part of the lipid membranes, but mimic only passive diffusion. All systems rely on flat membranes that have no resemblance to the small intestine and lead to a surface-to-volume ratio below the physiologic ratio of around 2 cm-1.In this research project, a physiological permeation model will be developed. Permeation membranes with structural resemblance to the wall of the small intestine will be created via 3D-printing. A bioprinter (CELLINK BIO X) will be used to print semisolid formulations to three dimensional membranes. The semi solid formulations will be based on polyvinyliden fluoride (PVDF) and polycarbonate. The PVDF membranes will be functionalized solely with lipids, the polycarbonate membranes will be cultivated with Caco-2 cells. These membranes will be tested in an established permeation model and will then be incorporated into a newly developed, three dimensional model of the small intestine. The resemblance to the real intestine will be further increased by incorporation a pumping system, which mimics the peristaltic flow pattern in the gut. The quality of the in vivo-in vitro correlation of the new systems will be evaluated against literature data. The aim of the research project is, therefore, the development and characterization of a physiological permeation model with high structural resemblance to the small intestine. This requires the development of membranes with defined three dimensional structure, the functionalization of the membranes, and the development of the model of the small intestine.

• DFG Programme: Research Fellowships
• International Connection: Sweden
• Host: Professorin Dr. Christel Bergström