Kyoto Prize Winner Robert Langer on Innovations to Come in Drug Delivery and Bioengineering

Xconomy Boston — 

The Kyoto Prize Symposium is now in full flower in San Diego, highlighting Japan’s highest international award for honoring the people who have made significant contributions to the scientific, cultural, and spiritual betterment of mankind.

The Kyoto Prize was first awarded in 1985, and for many it has become the most prestigious award available in fields that are not traditionally honored with a Nobel Prize. It also has become the only major international award with celebrations in two different hemispheres.

At an elaborate ceremony in Kyoto, Japan, on November 10, the three 2014 Kyoto Prize Laureates received their formal honors, which include a diploma, a 20-karat gold Kyoto Prize medal, and a cash award of 50 million yen (about $416,000 at the current exchange rate). The Kyoto Prize Laureates convened again in San Diego for a symposium that began yesterday and features free public lectures by three of the foremost scientists, engineers, and artists of our time.

Kyoto Prize medal (courtesy Inamori Foundation)

Kyoto Prize medal

As part of the celebration, I got an opportunity to put a few questions to Robert Langer, an Institute Professor at MIT (and a Boston Xconomist and prolific entrepreneur), who received the 2014 Kyoto Prize in Advanced Technology. The Kyoto Prize in Basic Sciences was awarded to Edward Witten, a theoretical physicist at Princeton’s Institute for Advanced Study; and the Kyoto Prize in Arts and Philosophy went to 89-year-old Fukima Shimura, a textiles artist best known as the creator of the tsumugi kimono.

Langer, 66, was cited as a founder of the field of tissue engineering, and for pioneering methods that use biodegradable polymers to form “scaffolds” upon which new tissues and even organs can be grown. Langer’s Kyoto Prize also notes his development for innovative and unique drug delivery technologies for the controlled release of medicines to directly target tumors and disease sites. Langer’s 2014 Kyoto Prize Commemorative Lecture in Advanced Technology is here.

Here is a condensed transcript of our conversation:

Xconomy: Was the Kyoto Prize awarded in recognition of your body of work, or was it for a particular accomplishment?

Robert Langer: I don’t know for sure because I wasn’t involved, but my sense from reading what they wrote was that it was for the body of work in drug delivery and tissue engineering… We’ve probably done a little more on drug delivery. Largely, what we’ve done is create new biomaterials for many different things, for drug delivery systems, nanotechnology, ways of creating new tissues and organs, and other things.

X: Could you sketch out some of the likely areas of innovation that you see in both drug delivery and in tissue engineering?

Robert Langer in Kyoto, Japan on Nov. 10.

Robert Langer in Kyoto on Nov. 10.

RL: In drug delivery, I think some of the really exciting things are in the area of nanotechnology, particularly with respect to enabling new kinds of drugs to be broadly useful… For example, delivering siRNA, delivering mRNA, some of the gene editing approaches. That’s one of the very, very exciting areas—targeted drug delivery and using nanotechnology to get the drug into your cells.

Other areas that are very exciting [involve] smart delivery systems. One example that we’re involved with is creating these intelligent microchips that can be put in the body, and someday have sensors on them, so they can deliver drugs in response to specific signals in the body.

A third area is what I call non-invasive delivery. Could you deliver large molecules or more complex molecules, by the oral route or the trans-dermal route, or pulmonary route? All those things are very exciting.

Finally, [an area] I think is very important is extending the kinds of things we’ve done in new ways for the Third World. Could you, for example, improve patient compliance by making vaccine delivery systems that you could inject once and get really high antibody titers [measurements]. There are many other areas as well where the work in drug delivery could really improve medical treatments in the third world. It’s quite vast, what the future holds, in terms of drug delivery systems.

X: Doesn’t the perennial challenge with drug delivery come down to figuring out ways to fool the body’s immune response?

RL: That is a challenge. Of course, it’s not like an all-or-none challenge. Sometimes you will get encapsulation. But that encapsulation is not sufficient to stop molecules from getting out of the capsule. With nanoparticles and micro-capsules, the drugs do come out, and of course there are now many products on the market based on these things, both injectable systems like Risperdal Consta that Alkermes makes and Lupron Depot that Takeda makes. Many of these last for many months. Even some of these birth control systems, like Norplant, last for many years.

With nanoparticles, there what you’re trying to do is often have it circulate and go in the right place in the body. There are strategies there too. We’ve done work and others have too in decorating those nanoparticles with a substance like polyethylene glycol that it make it harder for problems to occur.

Kyoto Prize Ceremony 2014 (courtesy Inamori Foundation)

Kyoto Prize Ceremony 2014 (courtesy Inamori Foundation)

X: There’s a company in San Diego that’s dealing with both of your areas of expertise. It’s called Viacyte. They’ve been developing an artificial pancreas that uses pre-pancreatic stem cells in a packet that is implanted just beneath the skin. The device allows the encapsulated pancreatic cells to release insulin and related hormones into the bloodstream.

RL: Diabetes, of course, is a more complex situation in that you are responding to something like glucose, and you want the drug to come out, you want the timing of that to be very precise. That’s actually an area that we’ve been working on in our lab as well. We have a large grant from the Juvenile Diabetes Foundation to try to come up with what we call super bio-compatible materials. I think we’re all excited to see how Viacyte’s results turn out.

X: They developed a mesh that prevents the white blood cells from coming in and attacking the pancreatic cells, but still allows insulin and other hormones to come out of the packet and into the bloodstream.

RL: A lot of people have tried to do this over the years. The goal on the one hand is to create a mesh or a pore structure that has a size that allows insulin and glucose to get through, back and forth, but won’t allow antibodies or macrophages to get through…There really are three challenges: One is to encapsulate the cells in a way that doesn’t hurt them. Two is getting the pore structure just right. And three is the bio-compatibility issue.

X: Could you also give us your overview of where innovation is taking place in tissue engineering?

RL: There’s a lot. Tissue engineering has gotten to be a very big area. Some of the innovations go across the board. What we just talked about with Viacyte is a great example of tissue engineering, because that involves cell therapies, with better materials; better design of systems that will enable diabetes treatment is certainly one area.
So there are many examples. They range from better cell-therapy kinds of approaches to basic research in learning how to control stem cell growth and differentiation. There are new materials advances, which could include what we just talked about with better materials and better compatibility. There are other properties that you want to do too.

For example, we have a big project with Steve Zeitels [of Massachusetts General Hospital] who is the surgeon for Julie Andrews and other singers. We’re trying to create gels that you could use to replace vocal cords, and that includes a whole range of properties that you want to have. That’s true across the board for any tissue or organ. You want to create just the right materials for that tissue or organ. If you try to make new vocal cords, that’s one set of challenges. New blood vessels is another set of challenges. Heart muscle, that’s another set. It goes on and on.

So what you see in tissue engineering are advances at a basic level, both in terms of understanding the cell therapies, and then in advances in materials to create new kinds of materials, and finally with each tissue or organ there are specific challenges that are critical in enabling you to ultimately make that tissue or organ.

Right now, there is FDA-approved skin, and we see in many cases various clinical trials going on in a lot of areas. For example, there are clinical trials going on to create new corneas, new spinal cords, new cartilage. There are many exciting areas going on with respect to individual therapies, and then there is this broader work that affects all of them.

Kyoto Prize Ceremony 2014 (courtesy Inamori Foundation)

Kyoto Prize Ceremony 2014 (courtesy Inamori Foundation)