Q&A: Controlled-Release Large Molecule Drug Delivery

Q1: What is controlled release drug delivery? Why is it important?

The judges have awarded the QEPrize for a technologically disruptive change in controlled-release drug delivery systems. Controlled release in drugs is important because a dose that is too high could be toxic, but a dose that is too low will not be effective. Controlled release drug delivery gives a patient the correct dose over a long period of time but requires much less frequent doses. For example, Bydureon® is the first weekly treatment for Type 2 diabetes.

Q2: What’s the difference between small molecules and large molecules?

In the area of pharmaceuticals, small and large molecule drugs are nominally differentiated based on their weight, with small molecules generally placed at less than 300 atomic mass units. However, they have many more differences. Because of their size and chemical properties, small molecules are relatively stable in the body and can cross cell membranes quickly and without assistance, easily reaching the active areas inside cells. Furthermore, some small molecules can cross through solid polymers. They stay confined and slowly leak out, leading to a steady dose over a long period of time. In contrast, large molecules are too big to do this and simply get trapped inside. Aspirin, with 21 atoms and a low molecular weight , is a conventional small molecule.

Small molecules are incredibly useful and make up the majority of available drugs. However, large molecules hold the key to tackling long-standing problems like cancer, mental illness, and diabetes. Unlike small molecules, they can attack specific cells and react in tailored circumstances, acting in the same ways as the body’s own proteins. Large molecules also have different chemical properties; they might have 20,000 atoms and be over 800 times heavier than aspirin. Furthermore, aspirin always has the correct structure. In contrast, the structure that a large molecule takes is vital to its function, and large molecule drugs are vulnerable to degrading and deforming when exposed to the body’s environment.

Q3: Why was Robert Langer’s work innovative?

Dr Robert Langer was a founding figure in the field of large molecule controlled drug delivery. His training as a chemical engineer and fundamental understanding of the sciences enabled him to make advances at the intersection of new materials synthesis and applied engineering. In a time when few, if any, engineers worked in experimental medical research, Langer’s perspective on medicine was unique: he saw surgery problems but created chemical and engineering solutions. Medicine at the time relied on existing, analogous materials. For example, dialysis tubing was made of cellulose acetate, inspired by its use in sausage casings. Polyether urethane, commonly employed as girdle elastic, was adapted for artificial hearts.

Langer turned this approach on its head. Instead of using what seemed convenient, he asked the engineering design question: what do you really want, from an engineering, chemistry, and biology standpoint? His answer was to synthesize exactly what was needed to solve problems. Not only did he solve the problem of large molecule drug delivery, he fundamentally changed the way that we use materials in medicine.

Q4: How is this innovation engineering?

Robert Langer translated engineering principles into human beings. He instituted a new, systematic, and rigorous engineering approach in medical material design. Starting with the engineering design question flowed naturally into considering and using engineering principles. The controlled delivery of large molecules in the complex environment of the human body relies on a thorough understanding and the precise application of engineering techniques and principles, including time-dependent design, modelling, reaction theory, and mass transfer.

Perhaps even more fundamentally, engineering is about two things: ingenuity, and problem solving. Experts and companies had dismissed this problem, but its solution needed real creativity and interdisciplinary collaboration. Ultimately, the clever solution lay at the intersection of many fields. Langer always kept the final goal in mind – as in much of engineering, he did exactly as much as was needed to solve the problem.

Beyond this, engineering is often called “the science of scale-up.” Langer started companies to see his ideas through from the lab to the patient. Without engineering, and its combination of new ideas and business savvy, these ground-breaking ideas would never have reached the people they were intended to help.

Q5: How did Dr Langer develop controlled release drug delivery for large molecules when so many people thought it was impossible?

Drug distribution systems existed prior to Langer’s innovation, but it was believed that slow, timed drug release was limited to small molecules. This was the standard view in fields ranging from medicine to polymer science.

Langer created a polymer and a system that overcame all of the long-standing challenges. Incorporating biomolecules into the creation of his polymer resulted in one that contained water-filled channels through which the large molecules could travel. Scientists were correct in believing that large molecules could not travel directly through polymers; but Langer gave them another path by applying an understanding of engineering phenomena. By engineering the channels such that they wound around in long, precise pathways, Langer could control the amount of time it took to disperse the large molecules. Faster systems are like walking through a park where the trees have all been planted in rows. Finding a way out is quick because the path is direct. In contrast, Langer’s paths are like trying to hike out of a forest filled with many, winding trails. He could design each path to take a certain amount of time. Additionally, the polymer itself broke down in a controlled fashion. It was another way to protect the fragile large molecules and release them at the correct rate, over as much as five years.

Q6: What else can be done with Robert Langer’s QEPrize-winning innovation?

Langer’s work was the basis for, among countless other innovations, long-lasting treatments for brain cancer, prostate cancer, endometriosis, schizophrenia, diabetes, and the drug-coated cardiovascular stents that alone have benefited 10 million patients.

Langer and many other researchers have extended his founding work into nano-medicine, tissue engineering, and to fields as diverse as agriculture and cosmetics. The 1000 patents that carry his name; the 300 pharmaceutical, chemical, and biotechnology companies that use his technology; the hundreds of his former students in engineering, chemistry, biology, physics, and medicine who now lead companies and labs around the world; and the 2 billion lives improved by the technologies that his lab has created serve witness to Langer’s unchanging goal of helping people, with engineering and science.