Midtveisevaluering - Ragnhild Haugse

ABSTRAKT

Innovative microbubble formulation for targeted drug-delivery using sonoporation

Sonoporation, the formation of pores in cell membranes caused by ultrasound and microbubbles, has great potential for use in targeted drug delivery of chemotherapeutics by enhancing the efficacy of chemotherapy without increasing side effects. The use of ultrasound in combination with the microbubbles is expected to increase extravasation of chemotherapeutics in tumour tissue and uptake of drugs into cells. Incorporation of drugs within microbubble will further ensure targeted release and delivery in a tumour using image-guided ultrasound alone. This could allow for smaller doses to be delivered, with higher localised concentrations resulting in reduced from systemic side effects. To take full advantage of this sonoporation concept we therefore suggest a new microbubble formulation: the antibubble. The ultrasound antibubble carrying drugs can be defined as a theranostic. Theranostic agent allow for combined diagnosis and treatment. Image-guided therapy by microbubbles and antibubbles loaded with drugs has a great potential for highly localised release and delivery of drugs. The acoustic properties of micro/anti-bubbles allow us to visualize tumour perfusion and release the encapsulated drug on- demand, within the tumour.

The main goals of this project are to optimize sonoporation-therapy and develop a new formulation for this use. We aim to investigate and optimize ultrasound and choice of microbubbles for efficient sonoporation for enhanced drug uptake.

Furthermore, we aim to unveil intracellular responses of sonoporation that further elucidates information on mechanism of action, and provide us with biomarkers for personalized therapy with sonoporation.

We will develop a novel sonosensitive antibubble drug carrier for site-specific drug delivery and imaging, including in vitro and in vivo testing of the newly developed antibubble. During formulation and optimization of the antibubble shell, influence of shell properties on sonoporation will be investigated.

(For more information: sonocure.w.uib.no)