Robert Langer has some impressive numbers to his name. The David H Koch Institute professor at MIT has published more than 1,350 papers, patented 1,100 innovations, co-founded 30 companies, won 220 awards and treated more than 20 million patients as a result of his inventions in smarter drug delivery. Langer is also the most cited engineer in history, a result of 40 years at the forefront of biomedical engineering, from his 1976 discovery of a method for the delayed delivery of large molecules1 to his recent work on the commercialisation of an implantable "pharmacy on a chip". He talks to WIRED about the future of drug delivery.
WIRED: Can you explain the ways in which a smart delivery system can improve the success of a drug?
Robert Langer: Three things are involved: safety, efficacy and compliance. In terms of compliance, sadly, fewer than 50 per cent of people take their drugs as prescribed, which is a problem in people with Alzheimer's, schizophrenia and other mental health diseases. This leads to more than $100 billion (£82bn) in costs. The New England Medical Journal showed that with hypertension in the US alone, around 100,000 deaths could've been prevented if people had taken their meds correctly.2 With safety, the problem with conventional delivery methods is that the level starts out low, spikes, then goes down. The spikes can be toxic, and when the drug level is too low, it's not effective. In terms of efficacy, sometimes you just can't get enough drug to the site with conventional delivery. With a targeted system, you can get higher amounts to where it's needed.
Can you describe the drug-delivery technologies you're developing to solve the compliance problem?
We're working on a long-acting pill that you could swallow to release the right drug dosage for weeks.3 This could stay in the stomach for a long time by using a polymer in the capsule that has "saved memory". When the capsule dissolves in the stomach, the material opens up to fix it in place until it degrades. And we can tune the degradation so this takes place on the set timescale. Compliance is an even bigger problem in the third world, so we're working with the Bill & Melinda Gates Foundation on using this with things like antimalarials. We also have a company, Lyndra, that's looking at Alzheimer's, so that rather than taking a pill four times a day, maybe you could take it once a month.
Much of your work in drug delivery comes out of one of your earliest discoveries around the use of polymers to distribute large-molecule pharmaceutical compounds. Can you explain the importance of this?
More new drugs are large molecules because they are more complex and contain more information. These could be peptides, proteins or antibodies, but the problem is that their structure deforms quickly in the body. Polymers allow you to get around this by delaying the drug's release over a longer period of time. But before we got involved, there were just a couple of types of molecules that could be delivered this way. The discovery that, by carving channels into the polymer, you could make this work with molecules of any size and any charge, opened the doors for the delivery of almost anything. To take one example, the peptide hormones that people want to use to treat cancer and endometriosis are too large to be absorbed orally - and if you inject them, they're destroyed right away. When put in the polymer systems, they can be continuously delivered over weeks, months or years.
How do you go about developing a polymer for a particular kind of drug and its delivery?
I'd break it down to a couple of parts: first, you can tailor the degradation rate of the polymer itself; second, the way you create the diffusion system. A lot of times, drugs get released not just because of the polymer's degradation, but because of pores or pathways in the material. You can control the size of these. We also try to use bio-compatible materials and, in many cases, we use combinatorial methods to synthesise new materials. We'll make thousands of these and screen them to select those that work the best. We've even made implantable microchips which let you regulate the delivery electronically to get a release when you want. Can you explain how this microchip drug-delivery system works, and where the idea for it came from?
I was watching a television show on how they make microchips and I thought, "If you could adapt something like that, wouldn't it be a great way to deliver drugs?" But I wasn't sure how to do it. I talked to my MIT colleague Michael Cima, who's a ceramics expert, and we developed a microchip with lots of little wells into which you could put drugs. Each of those wells has a cover that comes off whenever you send a particular radio signal to it.4
One of the things we're working on is a birth-control system that can be turned on and off if the user changes her mind, so she wouldn't need complex surgery to remove it. And we've already done a clinical trial with parathyroid hormone, which women are supposed to inject once a day for osteoporosis, but 77 per cent don't keep up with their injections. We're even thinking about mixing drugs - essentially a pharmacy on a chip - or allowing it to act as an artificial gland, regulating hormone levels in the body.
You were recently scientific adviser on an MIT Media Lab report calling for greater convergence of diverse research to solve medical challenges. How important has cross-disciplinary work been to your research?
It's been very important. Different people bring different perspectives and expertise. They also bring different ideas. So we could make a discovery about a new way you could do drug delivery, but then the question is, what do you want to use it for? Different clinicians and scientists have been very helpful to us in terms of developing potential applications.
For example, we invented this polymer that could dissolve evenly, like a bar of soap. Then Henry Brem, who's a neurosurgeon and chairman at Johns Hopkins, said, "Could you help us come up with a treatment for brain cancer?" So we created these brain-implantable polymer wafers containing an anti-cancer drug, and set up a company called GLIADEL to produce them. If you'd given that drug intravenously, it would travel all over the body and cause a lot of bad side effects. GLIADEL wafers have now been used all over the world for the past 20 years, but if I hadn't interacted with him, that would never have happened.
- Langer, R and Folkman, J, 1976. Polymers for the wSustained Release of Proteins and Other Macromolecules
\2. Ford, ES, Ajani, UA, Croft, JB, Critchley, JA, Labarthe, DR, Kottke, TE, Giles, W.H. and Capewell, S, 2007. Explaining the Decrease in US deaths from Coronary Disease, 1980-2000. New England Journal of Medicine, 356(23), p 2388-98.
\3. Lee, YAL, Zhang, S, Lin, J, Langer, R and Traverso, G, 2016. A Janus Mucoadhesive and Omniphobic Device for Gastrointestinal Retention. Advanced healthcare materials, 5(10), p 1141-6.
\4. Santini Jr, JT, Cima, M.J. and Langer, RS, Massachusetts Institute Of Technology, 2006. Microchip Drug Delivery Devices. US Patent 7,070,590.
This article was originally published by WIRED UK
