What will be the next breakthroughs in controlled drug release?

Controlled drug release has led to great strides in treating diseases, but it's only the beginning of what can potentially be achieved, says Prof Robert Langer

Controlled drug release has already transformed the way we treat serious diseases.  The method involves finding an effective way to gradually release drug molecules into a patient’s body through polymers.  The conundrum for scientists was that release the drugs too quickly and the treatment is at best ineffective, and, at worst, harmful.  Years ago, when I began my research in this field, a major problem was that drug molecules for many illnesses (cancer, for example) were too big to diffuse through the polymer.

My solution was to turn the problem on its head: instead of putting the drug molecules into a polymer, I layered the polymer around the molecules in a three-dimensional matrix structure that allowed the molecules to pass through slowly.

This research has already allowed scientists worldwide to take forward significant developments in treating disease.  The widely-available cancer drug Avastin, for example, is constructed in part on a bioassay based on ‘nanopellets’ – tiny polymer pellets that can be implanted directly into cancer tumours, to help stop new blood vessels feeding cancerous growths.

In 2008, I was privileged to be the third winner of the Millennium Technology Prize, the €1m prize awarded every two years by Technology Academy Finland for innovations which have solved great scientific and technological challenges and helped enhance peoples’ lives.  So, a decade on from winning the prize for controlled drug release – and as nominations open shortly for next year’s prize – what will be the next pioneering developments in this area?

Single dose vaccination for developing world applications is a Holy Grail

Firstly, the properties of polymers can be modified by external stimuli such as ultrasound, electric pulses or magnetic fields to change the release rate of the drug. This means the development of increasingly sophisticated release systems so, when combined with electronics on a microchip, the release rate can be programmed in advance so that the chip might deliver a carefully-measured dose of the medicine precisely when it’s needed.

This has huge potential benefits in a number of areas: for one, more effective birth control. We may someday see – subject to clinical trials – a microchip, implanted under the skin, being made widely available which will allow women to control their fertility levels via wireless remote.  The chip contains tiny reservoirs of the hormone levonorgestrel, already used in some contraceptives, and can dispenses 30mcg every day, holding enough of the hormone to do this for up to 16 years.  The possibilities are significant – not only in the Western world but especially in developing countries, where an estimated 220 million women have poor access to contraceptives and where around 80 million women had an unintended pregnancy, with one in four resorting to an unsafe abortion.

Eradication of polio is also potentially on the horizon.  A new nanoparticle vaccine that has been developed by MIT researchers that delivers multiple doses in just one injection, and could make it easier to immunise children in remote parts of the world where the disease is still found, in part because of the difficulty in reaching children in poorly accessible areas to give them the two to four polio vaccine injections required to build up immunity.

The single-injection vaccine is created by encapsulating the inactivated polio vaccine in PLGA (polylactic glycolic acid). This polymer can be designed to degrade after a certain period of time, allowing control when the vaccine is released.  Already one major obstacle that stymied previous efforts to use PLGA for polio vaccine delivery has been overcome: the problem of the polymer breaking down into glycolic acid and lactic acid that can harm the virus so that it no longer provokes the right kind of antibody response.

Eradication of polio is also potentially on the horizon

To prevent this from happening, the MIT team added positively charged polymers to their particles that act as “proton sponges,” soaking up extra protons and making the environment less acidic, allowing the virus to remain stable in the body.  As David Putnam, professor of biomedical engineering at Cornell University, has said: “Single dose vaccination for developing world applications is a Holy Grail, and they are getting close.”

Another breakthrough could be in treating diabetes, a condition that requires constant self-management, including lifelong, daily injections of insulin.  Today, most patients with diabetes will prick their fingers several times a day to draw blood and test blood-sugar levels and when needed, inject insulin. It’s an effective treatment but is often dosed incorrectly, leading to uncontrolled blood sugar levels. But technology based on research performed over the last decade looks set to change this, with the creation of a device that encases cells and protects them from the patient’s immune system. This can be combined with engineered cells that produce a target therapeutic, such as insulin. The devices are tiny hydrogel beads, about 1mm in diameter, which can be implanted into the patient through minimally invasive procedures.  This ‘living drug factory’ inside a patient’s body could deliver therapeutics, at the right amount and in the right location, as and when needed, and make daily injections obsolete, liberating millions of patients.

Controlled drug release has meant we’ve already made great strides in treating diseases ever more effectively.   The exciting thought, as these examples show, is that this is only the beginning of what can potentially be achieved.

Professor Robert Langer is Institute Professor at the Massachusetts Institute of Technology (MIT) and a scientist, entrepreneur and inventor.  Nominations for the 2020 Millennium Technology Prize open on 1 April 2019 and are accepted until 31 July 2019. More information is at www.taf.fi

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