While powerful drugs are available to treat certain types of cancers and cardiovascular disease, they are mostly administered as intravenous or oral doses, which limits control over their distribution in the body. With such "whole-body" dosing, the drugs can circulate in the patient's bloodstream and interact with many different tissues and organs, both diseased and healthy.
The SonoDrugs project will address this challenge by developing drug-delivery vehicles that can be tracked using real-time imaging and then triggered by focused ultrasound pulses to release the drug payload at the desired location. It's hoped that this controlled drug-delivery process will increase therapeutic efficiency and minimize side-effects, while also providing a means to tailor therapy to individual patients.
The drug-delivery vehicles will comprise nanoparticles (typically between 100 nm and 2000 nm in diameter) that can carry drugs to the site of disease via the bloodstream. Such small particles are easily transported by normal blood flow through the finest capillaries in the vascular system and can penetrate deep into diseased tissues.
The team will examine two particle types, the first of which has a shell made from a material that melts or becomes porous just above human body temperature (such as phospholipids, for example). The temperature rise required to melt the shell or increase its porosity - and thus release the contained drug - will be provided by the local heating effect of the focused ultrasound.
The second type of particle will be larger (up to 4 µm in diameter), with a shell that ruptures via pressure-induced stresses generated by the focused ultrasound pulses. Such gas-filled microbubbles are already in use as a ultrasound contrast agent and Philips Research has been investigating their application as a drug-delivery mechanism for several years.
The researchers also plan to employ two image-guidance modalities: MRI and ultrasound. MRI is ideal for use with thermally activated particles as it can be used to measure local tissue temperatures. It can also image soft tissues and locate particles labelled with MR contrast agents. Thus, MRI could be used to locate the target lesion and detect the arrival of the drug-loaded particles, and then provide accurate ultrasound focusing and controlled drug release using tissue-temperature measurements in a feedback loop.
The SonoDrugs project's work on MRI-guided drug delivery will focus primarily on potential treatments for cancer. Philips has already integrated the necessary ultrasound hardware and feedback mechanisms into its high-intensity focused ultrasound (HIFU) MRI research system using its phased-array ultrasound transducer technology.
For treatment of cardiovascular disease, the researchers will use ultrasound as the main imaging modality and as the means of releasing drugs from the particles. Here, the larger, pressure-sensitive particles will be used. This scheme is facilitated by the fact that gas-filled or partially gas-filled microbubbles show up well in ultrasound images.
"New therapeutic options such as externally triggered local drug release at the specific site of disease hold the promise to significantly improve patient care," said Henk van Houten, senior vice-president of Philips Research and head of Philips' healthcare research program.
"We realize that medical imaging technologies are only one of the enablers required to fulfil this promise," van Houten continued. "However, the wide-ranging expertise that has been brought together in the SonoDrugs project puts us in a strong position to ultimately deliver the benefits of image-guided drug delivery to patients and care providers."
• The SonoDrugs consortium comprises: Philips (the Netherlands, Germany, Finland); Nanobiotix (France); Lipoid (Germany); Erasmus Medical Center (the Netherlands); Universitäts Klinikum Münster (Germany); University of Cyprus (Cyprus); University of Gent (Belgium); University of Helsinki (Finland); University of London (UK); University of Tours (France); University Victor Segalen Bordeaux (France); University of Technology Eindhoven (the Netherlands); and University of Udine (Italy).
This story first appeared on our sister website, medicalphysicsweb.org