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Evaluating the circulation time of different formulations of microbubbles, continuation

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Microbubbles are clinically approved as contrast agents for ultrasound imaging for diagnostic purposes. There is however a strong research effort across the research community to use microbubbles as delivery vehicles for improved drug or gene delivery to a targeted diseases site. Cancer, atherosclerosis and various diseased in the central nervous system (CNS) are examples of diseases which might benefit from this research.

At NTNU and SINTEF there are a number of ongoing projects where we seek to improve the delivery of drugs (model drugs and cytostatic drugs) to tumor tissue and across the blood-brain-barrier by combining microbubbles, which are stabilized by nanoparticles containing drug, with ultrasound sonication towards the tumor. In order to achieve positive results we need microbubbles to circulate in the arterial system for a prolonged time. However, it has become apparent that the blood circulation time of the injected microbubbles depends strongly on the type of nanoparticle that is used when making the microbubbles.
In these experiments we will test the blood circulation time by ultrasound imaging of the heart, kidney, liver and/or large arteries in mice and rats for various formulations of microbubbles containing nanoparticles in order to validate the microbubble batches before they are used in extensive experiments with tumor-bearing mice.

All the described experiments are terminal and will be done under general anesthesia, hence it is not expected that the animals will experience pain or discomfort.

Other research projects involving the described microbubbles include both mice and rats, hence both species are included here. A total of 50 mice and 50 rats are expected to be needed. These experiments are important in order to reduce the chances of failing in experiments with drug delivery to animals with induced disease. Age, sex and strain are not of importance, hence we may use surplus animals from breeding or other experiments, thus reducing the total number of animals used at NTNU.