“Nanoparticle-based drug delivery can improve the safety and efficacy of existing drugs”

Dr Robert Langer
Dr Robert Langer was the first person to engineer polymers to control the delivery of large molecular weight drugs for the treatment of diseases such as cancer and mental illness. In an exclusive email interaction with Mahesh Kallayil, Dr Langer shares his insights on chemical engineering and its application in biopharma and the trends he observes in India.

Congratulations for winning the Queen Elizabeth Prize for Engineering. Request if you can elaborate the application of chemical engineering to medicine and biotechnology?
Chemical engineering is the key element in these areas: bioprocessing, pharma manufacturing, drug delivery, tissue engineering, gene therapy, medical device design and many others. It is a very broad discipline and I expect it to become even more significant in the future and contribute to vaccine delivery, neuroscience (eg, delivering drugs across the blood brain barrier) and areas that we cannot even imagine yet.

Can we have your thoughts on current trends in tissue engineering and regenerative medicine
There are a number- there are clinical trials ongoing in many areas including creating new blood vessels, spinal cord repair and many others. A lot of progress is going on in creating an artificial pancreas, new vocal cords, new intestine and others. An excellent basic research is going on in stem cell biology which will aid this field.

Could you please explain us in detail about your contribution towards polymer therapeutics and how it has transformed drug-delivery system?
Among other things we developed the first biocompatible polymer systems to continuously deliver large molecules first published in Nature. I like to think these early studies helped open the door for the long term delivery of many molecules. We also developed new polymers now used in treating brain cancer patients. We have advanced the concept of local drug delivery in cancer and other areas. Our lab has also made contributions in the areas of transdermal delivery, new aerosols and oral drug delivery systems.

Can you please take us through the accomplishments in the past in the field of nanotechnology and personalized medicine?
Compared to single molecule pharmaceuticals, drug containing nanoparticles have several potential advantages. They can have improved safety profiles to allow for higher doses that can minimize offtarget toxic effects while harnessing therapeutically desirable toxic effects, as in delivering cell-killing agents to cancer cells; offer prolonged delivery; combine treatments into synergistic and more efficacious treatments; allow for multiple targets to be turned off simultaneously; be combined with immunomodulatory approaches; and overcome drug resistance by concomitantly targeting multi drug resistance proteins.

Nanopart i c l e -containing drugs have already led to improved treatments. Paclitaxel-containing nanoparticles can be injected in much less toxic solvents than native paclitaxel, and nanoparticles containing doxorubicin show fewer adverse effects than the free drug. Targeted nanoparticles may be even better.

For example, targeted nanotherapeutics (containing potentially toxicdrugs) capable of finding diseased tissue and delivering treatment directly, ideally sparing the rest of the body from the potentially toxic substance, may improve safety and efficacy. In one case, nanospheres can encapsulate an anticancer drug using a coating, such as polyethylene glycol, that disguises it from uptake by immune cells. The coating also contains homing molecules (eg, antibody, aptamer) that have affinities with cell receptors but to a far lesser extent on healthy tissue. The polyethylene glycol coating allows the nanoparticles to circulate for long periods - sometimes days and the homing molecule helps them find the tumor. This approach is already in clinical trials with drugs like docetaxel incorporated in nanospheres.

Although nanoparticle-based drug delivery can improve the safety and efficacy of existing drugs, they may be even more critical to effectively using newer drugs based on methodologies such as small interfering RNA (siRNA) and messenger RNA (mRNA).

You turned away lucrative offers from oil companies in order to pursue your research in biotechnology. What lured you to this field?
I had been drawn to chemistry since I was a boy, and this led me to obtain BSc and ScD degrees in chemical engineering from Cornell University and MIT, respectively. While in graduate school, I hoped to use my background in chemistry and chemical engineering to improve people’s lives, so after earning my doctorate, I went into health-related research. This was against the norm in the chemical engineering field at the time, and most of my colleagues followed more traditional career paths, such as petroleum engineering, which was popular among chemical engineers.

Currently you hold more than 1060 granted or pending patents. In your opinion, what are the implications of IP in biomedical engineering?
They give leverage to raise funding which is key for doing the research. We have received a number of large industrial grants. We have also started a number of companies. This would not have happened without the patents.

As an impor tant founder of many bi o tech companies, what are the challenges one has to face as a biotech entrepreneur?
There are many. However, I would like to highlight the key ones like: raising funds, getting great business people and getting good intellectual property.

In the current scenario, Biopharma market in India is growing at an annual growth rate of 15% and by 2020, the market is projected to be worth over USD 200 Billion. As a biomedical engineer, how do you observe the steadily growing Indian Biopharma industry?
I’m certainly impressed to see the way things are going in India. The current scenario has improved drastically and people have realized the importance of engineering in India.

From a researcher’s perspective, how you think a Biopharma company can balance between research cost and making medicine affordable?
It’s critical to have enough funding to create new medicine and, unfortunately, at present, that’s a very expensive process.

What is your ultimate research goal in the coming 5–10 years?
My goals are to;
1) make new discoveries,
2) bring more of our earlier discoveries to the clinic and the 3rd world, and
3) training great future leaders.

What would be advisable for the upcoming potential engineers and researchers?
It’s a great career. Dream big dreams about how you change the world and make it a better place and then try to do that.