PhD defence T.T.K. (Trung) Nguyen

Stabilization and delivery of therapeutic proteins in the solid state

Toward a better shelf-life and personalized treatment with targeted delivery

Research towards the stability and the delivery of therapeutic proteins in the solid state and are the main subjects of the thesis of Trung Nguyen.

Nguyen: 'Firstly, we reviewed component distribution in the solid state with regard to its effect on the shelf life of proteins. The mechanisms behind the formation of inhomogeneous component distribution, the methods to analyze inhomogeneous component distribution, and ways to circumvent their negative effects were extensively compiled. Secondly, stabilizing capacity of arginine/pullulan combinations on the stability two model proteins after freeze drying and storage was studied.

Additionally, the mechanisms were elucidated why some arginine-pullulan combinations result in a different stability profile of the two proteins. These advances lead the way to better stabilize other biopharmaceuticals in the future.

Thirdly, the application of protein delivery was explored using 3D printing technology. The results showed that, after optimization, powder-bed printing of alkaline phosphatase stabilized in an inulin glassy matrix makes it possible to create customized dosages in the form of a tablet. Furthermore, a coating could be applied on the 3D printed tablet to enable release at the end of the small intestines allowing treatment of diseases in the large intestines.

Finally, the optimization of the tablet surface structure by 3D printing and post-processing method with ethanol further simplifies the production of such dosage form. This would ease the development process of future products using the same platform.

Overall, this thesis addressed some fundamental mechanisms regarding therapeutic protein stabilization in the solid state and explored the application of 3D printing on the delivery of these biopharmaceuticals.'

Promotores Prof.dr. H.W. Frijlink and Dr. W.L.J. Hinrichs