Ultrasound and delivery of drugs and nanoparticles
Ultrasound and delivery of drugs and nanoparticles to tumours
A major problem for successful cancer therapy using nanoparticles is the low and heterogeneous uptake of nanoparticles in tumour tissue.
Ultrasound has the potential of improving delivery of nanoparticles, and is found to be especially efficient in the presence of microbubbles. Under the exposure of ultrasound, the microbubbles being injected in the blood vessels will oscillate thereby inducing mechanical forces on the blood vessel wall. This will increase the transport of nanoparticles and drugs across the capillary wall and into the extracellular matrix.
The effect of ultrasound depends on several parameters such as ultrasound frequency, acoustic pressure, duration of the ultrasound pulse. Also the properties of the nanoparticles such as size and charge, and tumour characteristics such as vascular density, vascular permeability and cell density will determine the efficiency of ultrasound-mediated delivery. Using advanced imaging techniques, we are studying the effect of the various parameters to optimise the delivery of nanoparticles thereby improving cancer therapy.
Acoustic Cluster Therapy (ACT) for targeted drug delivery
Ultrasound-mediated delivery of drugs might be even more efficient using a novel concept called acoustic cluster therapy (ACT). ACT makes use of similar mechanisms as regular microbubbles, but addresses important shortcomings of the latter.
Regular microbubbles have a diameter in the range 2-6 μm. Thus, the magnitude of the biomechanical work they can induce is relatively limited. In addition, being free flowing they display limited contact with the endothelial wall, reducing the level and range of the biomechanical effects. Furthermore, microbubbles are typically cleared from vascular compartments within 2–3 min. The ACT formulation is a mix of negatively charged microbubbles and positively charged microdroplets, with the ensuing formation of microbubble/microdroplet clusters from the electrostatic attraction between the two components.
The ACT Cluster Dispersion for Injection may be co-administered with a regular medicament (e.g. chemotherapeutic) to induce locally enhanced uptake of the systemically injected drug. The clusters are small enough to be free flowing in the microvasculature after i.v. injection. When insonated with diagnostic ultrasound, the microbubbles transfers energy to the microdroplets that vaporizes forming bigger microbubbles. The 20-30 µm microbubbles are transiently deposit in the local microvasculature, stopping the blood flow for 5-10 minutes. Post activation, low intensity ultrasound is used to induce oscillations of the large bubbles ensuing biomechanical effects to allow for enhanced extravasation and distribution of drug molecules to the targeted tissue.
The concept is visualized in the figure. This project is done in collaboration with the company Phoenix solution.
Ultrasound and delivery of nanoparticles to the brain
We are investigating how microbubble combined with focused ultrasound can be used to find novel ways of transporting drugs and nanoparticles across the blood-brain barrier.
This is a prerequisite for treating diseases in the brain such as cancer and Alzheimer's disease.