A new way to deliver drugs with precise targeting

Most pharmaceutical products must be ingested or injected into the body to perform their work. Whatever the case may be, it takes them some time to achieve the intended goals and they also tend to spread to other parts of the body. Researchers from MIT and other countries have developed a system to deliver medical treatments that can be administered at specific times, minimally invasive, and that could also be administered in specifically targeted areas, such as a specific group of neurons in the brain.

The new approach is based on the use of tiny magnetic particles enclosed in a tiny hollow bubble of lipids (fat molecules) filled with water, called the liposome. The drug of choice is encapsulated in these bubbles and can be released by applying a magnetic field to heat the particles, thereby allowing the drug to escape from the liposome to the surrounding tissues.

The results are reported today in the diary Nature Nanotechnology in a post-doc of MIT Siyuan Rao, Associate Professor Polina Anikeeva, and 14 others at MIT, Stanford University, Harvard University, and the Swiss Federal Institute of Technology in Zurich.

"We wanted a system that was able to deliver a drug with temporal precision and could potentially target a particular location," says Anikeeva. "And if we do not want it to be invasive, we have to find a non-invasive way to trigger release."

Magnetic fields, which can easily penetrate through the body – as evidenced by the detailed internal images produced by magnetic resonance imaging or MRI – were a natural choice. The hardest part was finding materials that could heat up using a very small magnetic field (about one-hundredth of that used for MRI), to prevent damage to the drug or surrounding tissue, Rao explains.

Rao had the idea of ​​taking magnetic nanoparticles, which had already been shown to be able to be heated by placing them in a magnetic field, and placing them in these spheres called liposomes. They are like small lipid bubbles, which naturally form a spherical double layer surrounding a droplet of water.

When placed in a high-frequency but low-intensity magnetic field, the nanoparticles heat up, warming the lipids and subjecting them to a transition from solid to liquid, making the layer more porous – just enough to leave escape some of the drug molecules into the surrounding areas. When the magnetic field is turned off, the lipids solidify again, preventing any subsequent release. Over time, this process can be repeated, releasing doses of the included drug at precisely controlled intervals.

The drug carriers were designed to be stable inside the body at a normal body temperature of 37 degrees Celsius, but able to release their load of drugs at a temperature of 42 degrees. "So we have a magnetic switch for drug delivery" and this amount of heat is small enough "not to damage tissue by heat," said Anikeeva, nominee in the materials science departments, engineering and civil engineering. Brain and Cognitive Science.

In principle, this technique could also be used to guide particles to specific locations in the body, using magnetic field gradients to push them, but this aspect of the work is an ongoing project. For now, researchers have injected the particles directly into the target areas and used magnetic fields to control the timing of drug release. "The technology will allow us to address the spatial aspect," says Anikeeva, but this has not yet been demonstrated.

This could allow very precise treatments for a wide variety of conditions, she says. "Many brain disorders are characterized by erroneous activity of certain cells.When the neurons are too active or are not active enough, this results in a disorder such as Parkinson's disease, depression or epilepsy." If a medical team wishes to administer a drug to a specific group of neurons and at a given time, for example when a symptom appears, without subjecting the rest of the brain to this drug, this system "could give us a very good way to deal with these conditions, "she says.

Rao says that making these liposomes activated by nanoparticles is actually a fairly simple process. "We can prepare the liposomes with the particles in a few minutes in the lab," she says, and the process should be "very easy to adapt" for manufacturing. And the system is broadly applicable to drug delivery: "we can encapsulate any water-soluble drug," and with some adaptations, other drugs as well, she says.

One of the keys to developing this system was to perfect and calibrate a way to produce liposomes of extremely uniform size and composition. This involves mixing a water base with lipid molecules of fatty acids and magnetic nanoparticles and homogenizing them under precisely controlled conditions. Anikeeva compares the fact of shaking a bottle of vinaigrette to mix oil and vinegar, but controlling the timing, direction and strength of agitation to ensure accurate mixing.

Anikeeva explains that while his team specializes in neurological disorders, the drug delivery system is actually quite general and could be applied to almost any part of the body, for example to administer anticancer drugs. or even painkillers. directly on an affected area instead of systematically administering them and affecting the entire body. "It could deliver it where it is needed, not continually," but only as needed.

Since the magnetic particles themselves are similar to those already widely used as MRI contrast agents, the regulatory approval process for their use can be simplified, as their biological compatibility is largely proven.