Sneaking medications past our bodies’ blood-brain barrier has always been a tricky proposition. The barrier – essentially a filter between the brain the blood vessels supplying it – blocks the passage of most substances. It’s generally considered a good thing because it protects the brain from blood-borne infections and toxins. However, when it comes to drugs designed to target brain-based diseases, that barrier is a liability.
Which is why McMaster University chemical engineer Todd Hoare recently teamed up with a group of neuroscientist colleagues to make a nasal spray to bypass the barrier and deliver an antipsychotic drug directly to the brain.
Usually, people with schizophrenia, bipolar disorder and other conditions take their medication in pill form or injections. This means they must take more than their brains need so that at least some of it slips through the barrier.
But with a nasal spray, the drug can take a shortcut to the brain and patients can significantly cut back dosages. This in turn could help to reduce the drugs’ often nasty side effects, including weight gain, diabetes, movement disorders and organ damage.
Hoare’s contribution was coming up with a vehicle for getting the medication to the brain via a nasal spray. His solution involved tweaking corn starch nanoparticles made by Burlington-based EcoSynthetix – particles he had been investigating for agricultural applications.
“They are super small – in the 20 to 30 nanometer range – and can swell in water but remain stable,” he says. “They can help soil retain water during drought and can help with the timed delivery of fertilizers and pesticides.”
The serendipity of science
It was only after a researcher in his lab attended a conference and met a researcher in the lab of Ram Mishra from the Department of Psychiatry and Behavioural Neurosciences that Hoare realized his nanoparticles could be the perfect delivery system for Mishra’s experimental drug.
“They didn’t know what we were working on and we didn’t know what they were working on. The match-making was fortunate,” he says.
As Hoare discovered, Mishra and his team had created a water-soluble form of an anti-psychotic medication and while it easier to manipulate, they lacked an effective way to get it to the brain. Mishra had considered a nasal spray but was concerned that drugs delivered through the nose tend to clear from the body quickly, requiring frequent re-administration. People who take anti-psychotic medication often struggle to adhere to a regular dosage schedule, leading to significant relapses.
“Anything that reduces the need for a patient to administer the drug frequently may have other benefits in terms helping patients stick to their medication regime,” says Hoare.
So, he and his team came up with a solution that allowed for the gradual release of the drug – a nanoparticle drug delivery system that starts with corn starch nanoparticles.
“We do a lot of fancy chemistry in our lab,” says Hoare. “But there was very little chemistry we had to do with this.”
First, he and his team lightly oxidized the particles to allow the peptide drug to stick better to the starch. This also allowed the researchers to covalently bond the starch with carboxymethyl chitosan, a natural polymer derived from crabs.
When the mixture was aerosolized, it could penetrate deep into the nasal cavity and form a thin gel in the mucus lining. Because the covalent bond between the starch and the carboxymethyl chitosan is relatively reversable, the gel degrades in the nose’s moist environment.
In tests with rats, it slowly released a controlled dose of the drug that controlled schizophrenic symptoms for at least three days after a single spray.
While nasal sprays are sometimes used to deliver medications, not many are gels that can be sprayed. The advantage is that it sticks to the nose’s mucus lining better and degrades more slowly than non-gel sprays.
Hoare and Mishra are now looking for partners to conduct human trials and are hopeful that the simple chemistry involved in the nanoparticle delivery system will work in their favour.
“The less complicated you can make it, the better chance you can get it approved,” says Hoare.