New nasal spray conveys antipsychotic medicine straightforwardly to the brain
- Post By : Kumar Jeetendra
- Source: McMaster University
- Date: 17 Jan,2021
A team of neuroscientists and engineers at McMaster University has made a nasal spray to deliver antipsychotic medication directly to the mind rather than having it pass through the body.
The jump in efficiency means patients with schizophrenia, bipolar disorder and other conditions could see their doses of powerful antipsychotic drugs cut by as much as three quarters, which is expected to save them from sometimes-debilitating side effects while also significantly reducing the frequency of mandatory therapy.
The new method delivers medication in a spray that reaches the brain directly through the nose, offering patients greater ease of use and the promise of improved quality of life, including more reliable, effective treatment.
They and their co-authors Michael Majcher, Ali Babar, Andrew Lofts, and Fahed Abuhijleh have proven the concept of their new delivery mechanism in rats, using PAOPA, a medication commonly prescribed to treat schizophrenia.
The trick here is to administer the drug through the back door to the brain, since the front door is sealed so tightly. This way we can bypass the blood-brain barrier. By delivering the drug directly to the target, we can avoid side effects below the brain.”
Ram Mishra, Professor, Department of Psychiatry and Behavioural Neurosciences and Co-Director of McMaster’s School of Biomedical Engineering
A problem for patients using antipsychotic drugs, Mishra explains, is that taking them orally or by injection means the drugs must pass through the body before they reach the brain through the blood. To be sure enough oral or injected medication reaches the mind, a patient should take considerably more than the brain will ultimately get, resulting in sometimes serious adverse side effects, including weight gain, diabetes, drug-induced movement disorders and organ damage over the long term.
When delivered via the nose, the spray medicine can enter the brain directly through the olfactory nerve.
Mishra and collaborator Rodney Johnson of the University of Minnesota had created a water-soluble form of the medication, which was utilized in the current research. The new form they created was easier to control, but they still lacked an effective vehicle for getting it into the mind. A specific issue was that drugs delivered via the nose are generally removed from the body immediately, requiring frequent re-administration.
Hoare, in the meantime, was working with an industrial partner to develop the use microscopic nanoparticles of corn starch for agricultural applications.
Both scientists, who work across campus from one another, came together after researchers in their labs fulfilled at an inner McMaster conference.
The engineering team was able to bind the drug to the corn starch nanoparticles that, when sprayed together with a natural polymer derived from crabs, could penetrate deep into the nasal cavity and form a thin gel in the mucous lining, slowly releasing a controlled dose of the drug, which stays effective for treating schizophrenia symptoms over three days.
“The cornstarch nanoparticles we were using for an industrial application were the perfect car,” Hoare says. “They’re naturally derived, they break down over time into simple sugars, and we will need to do very little chemistry on them to make this technology work, so they’re great candidates for biological uses like this.”
The gradual release means patients would just have to take their medication every couple of days instead of every day or, in some cases, every couple of hours.
Majcher, M.J., et al. (2020) In situ-gelling starch nanoparticle (SNP)/O-carboxymethyl chitosan (CMCh) nanoparticle network hydrogels for the intranasal delivery of an antipsychotic peptide. Journal of Controlled Release. doi.org/10.1016/j.jconrel.2020.12.050.