28 April 2010

Drug delivery: tablets of the future are ready for testing

Trojan Pill
The pill of the future has already been created – its action in the human body can be controlled from a distance

Alla Astakhova, "Results", 04/26/10.

It was an age–old dream of physicians to create an ideal pill that would begin to act in the patient's body not immediately, but at the moment when the medicine reaches the diseased organ or when the doctor's deadline comes: in a day, a week, a month or even a year... It looks like a dream come true. Clinical trials of biopolymer capsules intended for targeted drug delivery to the body will begin in the near future. They have already been dubbed the pills of the future. Gleb Sukhorukov, the author of the discovery, our compatriot, head of the biopolymer group at the Faculty of Materials Science at Queen Mary College of the University of London, told The Results about the essence of the discovery.

– Gleb Borisovich, did the pill of the future have a difficult past?

– It all started almost two decades ago, during my graduate work at the physics faculty of Moscow State University. I came to chemists who were engaged in electrolyte complexes with the idea of making the thinnest polymer films similar to puff pastry – their thickness would be regulated by layers of either positively or negatively charged polymer in fact into one molecule. Now we know that the properties of such films are programmed: if the film is thicker, then its permeability will be less, and vice versa. The behavior of the film can be controlled. If we include in its composition a polymer that is able to expand with changes in acidity or temperature, exposure to light or electromagnetic field, respectively, the entire film or capsule made of it will expand or contract at a certain time, absorb something or release, or even collapse. By including natural substances in it – proteins, enzymes, it is possible to achieve certain reactions. Up to the point of modeling an artificial cell. That is, to create a tiny device for a variety of applications.

– Did you mean a smart pill wrapper?

"I didn't think about it then. Moreover, at first there were doubts that such films could be created at all. Chemists explained to me that from the point of view of fundamental science, these layered thinnest polymers cannot be built, they should not be obtained. And theoretically they are still right. There really shouldn't be such films in an equilibrium system. But the fact is that in practice we always operate with non-equilibrium, metastable systems. From the point of view of fundamental science, what we are doing does not seem to be quite right, but nevertheless it turned out to be possible to assemble such layered films.

– When did you come up with the idea to assemble medical capsules from films?

– It happened 12 years ago. I then defended my dissertation and worked in Germany in the Max Planck institute system. My colleagues and I already knew how to make these films on a flat surface, but we haven't thought about their application yet. And one day we just decided to collect them into balls, thinking that then we could study them by other methods. And suddenly they discovered that the properties of these films on a three-dimensional surface give them the opportunity to expand, launch something inside, release it outside, and contract again. So for the first time the idea of an ideal controlled pill dawned. Of course, it wasn't easy. We learned how to encapsulate various substances only 5 years ago.

Capsules nested one into another, like in a matryoshka doll.
As needed, their shells can be opened in turn, one after the other
Photo: Gleb Sukhorukov (from the personal archive)

– Have you tried them in action yet?

– We decided to inject capsules into cancer cells. At first it was purely a research interest. And cancer cells were taken for one simple reason: because of their "voracity". They grow very quickly, and virtually everything that is near them or on their surface immediately turns out to be inside them. The same thing happened with our capsules. So it turned out that they are able to get inside the cell. Later, for certain purposes, we used the same "voracity" of immune cells, macrophages. Now, with the help of our capsules, an American company is developing in the field of immunology. The fact is that there are certain proteins-antigens that do not cause an immune response until they get into the cell of the body. We have found a solution: we can make a capsule – a "Trojan horse". It will enter the immune cell, then under the action of cell enzymes or some external influence, the polymer shell will disintegrate (this process can be programmed), and the released antigen proteins will trigger an immune response.

A cancer cell with capsules inside
Photo: Gleb Sukhorukov (from the personal archive)

– How can you influence a capsule already in the body?

– It turned out that a lot can be achieved by placing nanoparticles in a capsule. Let's say the thickness of the capsule shell is 50 nanometers. Magnetic nanoparticles 10-20 nanometers in size fit perfectly there. If a capsule with a large number of such nanoparticles is placed in a magnetic field, it will begin to move, and its movement can really be controlled. So it is possible to remove drugs from the tissues of the body that were not needed. Another example: metal nanoparticles of gold or silver heat up well under the influence of light. If we make the capsule shell 20-30 nanometers thick, it will burst as a result of such heating and at the moment when we want it, it will release the medicine in the capsule.

– Does this mean that any properties can be given to the shell?

– Absolutely. It's like a children's constructor. Using different principles of elementary assembly of polymers, we can "sew" completely different functions there, of which there can be many – sensitivity to the magnetic field, to light, to acidity, to temperature, in principle to anything. By the way, in experiments with cancer cells, the property of magnetic nanoparticles to heat up locally under the influence of electromagnetic radiation was used. They took capsules with such nanoparticles, delivered them to cancer cells, and they burned out, burning out the tumor. If there was medicine in the capsules, at that moment it would enter the body.

– Do you have competitors in this scientific field?

– There are many ways to deliver medicines in the world. Our technology has a disadvantage: it is more expensive than many. However, there are problems that only we can solve so far. For example, DNA and a certain protein or several different DNA must be delivered to the same cell of the body at the same time. Now we are already conducting research projects with biologists – with the help of our capsules, we can try to influence the differentiation of stem cells. It is known that so far this is a stumbling block for those who are going to develop cell therapy. It is very difficult to control the process of cell differentiation. But we can put a capsule with the right substances in the cell, which will sleep in it until the right time comes. And then we will open the capsule remotely using light or the same magnetic field.

– What is more difficult now: to look for money for development or like-minded people among doctors or biologists?

– Both are difficult. I admit, the flow of development funding has now significantly decreased. If earlier it took half a million euros a year to maintain the work of our laboratory, now we have to make do with less. However, the main problem is different. It is much more difficult and important to find the right people to cooperate with them. We need a doctor who is interested in the topic, who will not be afraid to work with us and set tasks. For example, there is a risk of complications after surgical operations. And here capsules with an antibiotic would help – they can be placed in the cavity in advance and activated only if necessary. And if not, remove the medicine from the body in small doses for a long time. Now we are considering this possibility with the doctors.

– Should we expect concrete results in the near future?

– This year, for the first time in China, trials of the delivery of drugs placed in our capsules – interferons, erythropoietins - to the body should begin. Preclinical experiments on animals are going in different directions.

– Do you consider yourself a representative of nanoscience?

– There is no nanoscience as such – it is a set of methods and knowledge, I always tell my students so. Today, ideas expressed thirty years ago are being fired. Methods have appeared in biology, chemistry, and physics, with the help of which humanity has learned to "play" with molecules, make nanoscale structures, and control them. In fact, the word "nanoparticles" appeared about 15 years ago, and earlier, in the Soviet literature of the 60-70s, they were called "ultrafine particles", that is, the phenomenon was known. It's just that electron microscopy was poorly developed, there were no other methods of observation. Now everything has appeared – this is the reason for the boom. The moment has come when it has become possible to do a lot in this area.

Portal "Eternal youth" http://vechnayamolodost.ru28.04.2010

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