PhD defence K.B.A. (Kornelis) Meijlink

Below is a brief summary of the dissertation: 

Delivering drugs specifically to diseased tissue can improve treatments and reduce side effects, for example, in cancer and cardiovascular diseases. A new technique uses microbubbles, tiny gas bubbles with a lipid coating, which vibrate when exposed to ultrasound. These vibrations help drugs pass through blood vessel walls and cell membranes, allowing them to reach the underlying diseased tissue. This dissertation investigates how these processes work to ensure the technique can be safely used in hospitals.

We discovered that microbubbles with a specialized coating are internalized by cells and create pores in cell membranes more quickly, despite vibrating less strongly. Sometimes, they even create tunnels through cells. F-actin, the cytoskeleton, plays a crucial role in this process. Additionally, we observed that disruption of specific F-actin structures by microbubbles causes openings between cells, promoting drug delivery. Using a “vessel-on-a-chip” model, a mini-blood vessel made from human cells, we studied which ultrasound parameters are most effective. Higher ultrasound pressure and longer cycles increased drug delivery without causing damage. These results were confirmed in live chicken embryo blood vessels, although additional effects, such as vasoconstriction, were observed in the living model. Finally, we investigated how different types of microbubbles affect drug delivery. Microbubbles with a more evenly distributed lipid layer adhered more strongly to cells, improving targeted treatment. Additionally, smaller microbubbles were found to be nearly as effective as larger ones.

Conclusion: The use of microbubbles and ultrasound shows great promise for safe and targeted drug delivery, potentially improving treatments and reducing side effects.