Interview with Patrick Couvreur, nano-oncologist and professor at the Paris-Sud University. He and his team won the 2013 European Inventor Award in the Research category for their work on nanocapsules.

[Portrait of an Innovator] Patrick Couvreur develops nanotechnologies for delivering therapeutic drugs to specific areas of the body

An innovator? Yes. And the list of discoveries in the pharmaceutical field made by this scientist, who originally hails from Belgium, is a long one. From 2009 to 2010 he held the Liliane Bettencourt Chair of Technological Innovation at the prestigious higher education and research establishment Collège de France in Paris and the same year received the Galien prize for innovation in pharmaceutical treatments, also obtaining a €2.2 million grant from the European Research Council to pursue his research into nanomedicines. Three years later, in 2012, he received the Innovation Medal from the CNRS, the French National Centre for Scientific Research. His most recent accolade is the European Inventor Award. Patrick Couvreur is recognised worldwide for his work on the use of nanoparticles to deliver drugs to specific areas of the body. He first began to work on nanoparticle technology during his post-doctoral studies between 1977 and 1983. “Up to then, the use of nanotechnology had been focused on vaccination. I was interested in using the technology to deliver therapeutic substances to the exact place where they were needed. So I began to work on creating nanometric capsules able to penetrate cells to deliver specific molecules – drugs or sometimes coloured test substances, which did not otherwise naturally reach the right spot.” At the end of this period, encouraged by the initial results, he decided to pursue research in this field.  However, “the technique that we had developed used a non-biodegradable polymer, a type of nylon, and it was unthinkable to use that for clinical purposes. We simply couldn’t inject it intravenously into a patient.”  He therefore set out to develop a nanoparticle using a biodegradable polymer. In 1984, he joined the faculty at Paris-Sud University, working alongside Professor Francis Puyeux, and set up a research unit on Physical Chemistry, Pharmacology and Biopharmacy, under the aegis of the CNRS, which he is still running many years later. “At that time, pharmaceutical design was seen as a purely technical process, a sub-field of biochemistry, and it was quite some time before it was recognised as a subject in its own right.”


The disruptive idea? In 2013, Patrick Couvreur received the Innovation Medal for a ground-breaking discovery he made. “Up to that point in time, everyone used to encapsulate nanoparticles physically inside liposomes*,” points out the nano-oncologist.  However this technique has its limitations.  The potential therapeutic load is very low, of the order of 1%. So every 100 ml of delivery material contains just 1mg of the drug. Which means that “either you don’t achieve sufficient concentrations at the target area – cancerous cells for example – or you raise the dose and then you have the toxicological drawbacks.” The second limitation when encapsulating the therapeutic substance is that part of the medicine isn’t contained in the core of the nanoparticle but is simply absorbed into its surface.  “And so when you inject the drug into the patient, this part will be immediately liberated without ever getting near the affected cells, quite apart from the side effects this might produce,” he explains, underlining: “This is why there aren’t more nanomedicines on the market.” Faced with these two technical obstacles, Professor Couvreur and his team set out to raise the delivery rate. “We began to concentrate on chemical, rather than physical, encapsulation.”  The technique here consists in taking a delivery molecule and chemically binding it with a molecule of the drug. “This means that every delivery molecule carries a molecule of the drug.” The challenge was to find a delivery substance capable of spontaneously forming nanoparticles on contact with water. “At that moment we had the idea of using squalene, a natural, biocompatible lipid which we all already have in our bodies, and which has an extremely compact molecular configuration. So as soon as you bind it with a drug molecule – anti-viral, anti-cancer, anti-infection, etc – this bioconjugate forms nanoparticles upon contact with water.”  The tests carried out by Professor Couvreur’s team revealed that these nanoparticles carry a much higher therapeutic load, as high as 50%, versus the 1% achieved up until that time. Apart from the fact that this requires less delivery substance to be administered, which means a lower toxicological risk, this discovery meant that a specific area of the body could be targeted.  The chemical bond between the therapeutic drug and the squalene will not be broken before it reaches the cancerous cells.


What’s the most interesting aspect? “For a long time the modus operandi had been to do the basic chemistry, discover new molecules and synthesise drugs”. Patrick Couvreur decided to break with this approach, which had “reached the end of the road”. He was firmly convinced that it was feasible to “take old molecules which have their disadvantages in terms of biodistribution, biodisposition, clinical pharmacokinetics and lack of selective effects, but whose pharmacological and toxicological characteristics were already known.” You can then bind these molecules with nanovectors so as to deliver them in a much more targeted way from the pharmacological point of view. This technique can be applied in a number fields – imaging, treatment of infectious diseases in immuno-depressive patients, and so on – but Couvreur’s work has focused to a large extent on cancer treatments. ”I really do think this is a field where we need to develop new therapeutic methods. Not that the existing therapies are ineffective but they do have dreadful side effects.” The reason is very simple: “When you administer a drug to an organism intravenously, it will impregnate all the organism’s cells, not just the tumerous tissue.  So you have to increase the dose in order to attain a sufficient concentration in the tumerous tissue and then you very soon encounter toxicity problems in the rest of the body.


So what’s the impact of all this? What the pharmacological experts call ‘drug vectorisation’ is proving to be a more effective approach. It’s more targeted, less toxic in its effects and improves patient tolerance. Today fewer and fewer new molecules are being synthesised. We are witnessing “a decrease in innovation in the drugs field,” reveals Couvreur. However, the chemical encapsulation approach is now enabling hitherto untreatable cancers to be treated by targeted delivery of the drug, which helps to overcome some of the body’s resistance mechanisms.  A range of applications are feasible in the field of vaccination, diagnostics and to treat infections in people suffering from immunodeficiency, for whom the traditional way of administering drugs has no effect.  


And what does the future hold? “Continue the research and try to develop the technology for applications such as treatment of cancer of the pancreas.”


*liposome: an artificial vesicle formed by concentric double lipid layers which trap aqueous compartments between them