Chewing gum is often considered a bit of a social faux pas, but you may have a good excuse in future. Instead of taking medication by tablet or injection, chewing gum is set to be an alternative drug delivery route. Nicotine gum is already a convenient way for would-be quitters to handle their cravings. But pharmaceutical companies are looking beyond nicotine replacement products and exploring other indications that medicated gum could help, from diabetes to pain relief.
Delivering medication via chewing gum could have several advantages over conventional tablets, explains mechanical engineer Dr Kazem Alemzadeh from the University of Bristol. The biggest benefit is that the drug can be absorbed through the gums, cheek and tongue and avoid being broken down in the gut.
It potentially means a lower dose of the medication could be prescribed compared to a pill. Other pros for medicated gum include easy administration – good news for people who hate swallowing tablets. There’s no need to take it with water and medicated chewing gum can potentially provide sustained drug release over time.
Alemzadeh believes medicated gum could even represent a solution to the opioid abuse crisis. In the US, 175 people die every day from overdosing on opioid painkillers, while deaths caused by opioid fentanyl are on the rise in the UK, warned the Advisory Council on the Misuse of Drugs in January.
“People who are addicted get these cheap painkillers, crush them, melt them and inject them into their body,” he says. “If these tablets were chewing gum, they can’t do it. They can’t abuse it. It’s as simple as that.”
No gold standard
That said, there are some key reasons why medicated chewing gum hasn’t taken off in the pharmaceutical industry. The major barrier is that scientists are currently unable to replicate human chewing in the laboratory, which means there is no gold standard for testing drug release kinetics of medicated gum.
This could be set to change. Alemzadeh has been working on developing a robot that can chew gum just like a human. The project began in 2009, when he presented an invention at the Royal Society. His robotic simulator evaluated restorative materials used to treat dental problems. It attracted the interest of US chewing gum giant Wrigley, represents of which visited Alemzadeh in Bristol to ask if his robot was able to chew gum.
“I told them, ‘I’m afraid not’,” says Alemzadeh. “But I started digging around and found that the pharmaceutical industry is spending a colossal amount of money to develop medicated chewing gum.”
He discovered companies such as Generex Biotechnology, which was looking to develop a chewing gum for people with diabetes that contained blood sugar-lowering drug metformin. But organisations fell short when it came to testing the product.
“There is no instrument in the world which can test the medicated chewing gum for the release of the drug and determine the dose,” explains Alemzadeh, pointing out that the two machines that currently exist can’t accurately mimic the chewing action of a human and so haven’t gained FDA approval. “But my robot can chew like you and me.”
Replicating the human jaw
Building a robot to simulate the mechanics of the human jaw isn’t easy. The mouth is a remarkable feat of engineering. It contains a lower jaw (mandible) and the upper jaw (maxilla) which are connected at the temporomandibular joint. Unlike other joints in the body, the temporomandibular allows six degrees of freedom.
A chewing robot should replicate not only the anatomical features but the motion of chewing and food processing. Alemzadeh has mechanised these characteristics and his robot even includes artificial saliva. The device is capable of closely replicating the human chewing motion in a closed environment.
“There are three things happening in sequence,” explains Alemzadeh. “First you shear the food, then you crush it, and then you grind it. And all of these will happen in 0.2 seconds. It’s amazing: you do it automatically and without biting your tongue at all.”
Next, he needed to see how the robot fared against human volunteers. Working with a team of Bristol Dental School researchers led by Professor Nicola West, they measured the amount of xylitol (a sweetener found in chewing gum) remaining after a period of chewing.
Saliva from human participants and artificial saliva from the robot were collected after five, ten, 15, and 20 minutes of continued chewing so the scientists could establish how much xylitol had been released.
The team was able to demonstrate that the robot jaw had a similar release rate of xylitol as the human mouth. And the greatest release of the sweetener occurred during the first five minutes of chewing. After 20 minutes, only a small amount of xylitol remained. The study is published in IEEE Transactions on Biomedical Engineering.
“The most convenient drug administration route to patients is through oral delivery methods,” said West in a statement. “This research, utilising a novel humanoid artificial oral environment, has the potential to revolutionise investigation into oral drug release and delivery.”
Having successfully demonstrated that a chewing robot can closely replicate human mastication, Alemzadeh is applying for funding grants from the EPSRC and MRC to further validate the device using nicotine gum. He hopes the next step is to partner with a pharmaceutical company to test a medicated gum in early development using the machine.
“In vitro, the analysis of the chewing gum is very hard to quantify but we’ve proved with this machine you can do it,” he says. “This is just the beginning. My message to the pharmaceutical companies: come on board and test a new drug.”