Tag Archives: nanoparticle nasal spray

Brain stimulation combined with a nose spray containing nanoparticles can improve stroke recovery (in an animal model)

A September 28, 2022 news item on Nanowerk announces research into combining nasal sprays and brain stimulation in efforts to improve stroke recovery (Note: A link has been removed),

In a recent study (Materials Today Chemistry, “Enhancing non-invasive brain stimulation with non-invasively delivered nanoparticles for improving stroke recovery”), researchers from Xi’an Jiaotong-Liverpool University and other universities in China have reported that brain stimulation combined with a nose spray containing nanoparticles can improve recovery after ischemic stroke in an animal model.

The nasal spray is a non-invasive method for delivering magnetic nanoparticles into the brain that the study finds can increase the benefits of transcranial magnetic stimulation (TMS). TMS is a method of non-invasive brain stimulation already used clinically or in clinical trials to treat neurological conditions like stroke, Parkinson’s disease, Alzheimer’s disease, depression, and addiction.

I have two previous posts about nasal sprays and nanoparticles (links to previous posts follow at the end) but this item is the first to include brain stimulation. From a September 27, 2022 Xi’an Jiaotong-Liverpool University press release (also on EurekAlert but published on September 28, 2022), which originated the news item,

Rats that were given combined nanoparticle and TMS treatment every 24 hours for 14 days after an ischemic stroke had better overall health, put on weight more quickly and had improved cognitive and motor functions compared to those treated with TMS alone.

During TMS treatment, an electrical current runs through an electric coil placed outside the skull, producing a magnetic field that stimulates brain cells by inducing a further electrical current inside the brain. However, the stimulation is often not intense enough to penetrate far enough into the brain to reach the areas needing treatment. 

In this new study, the researchers show that magnetic nanoparticles, administered intranasally, can make neurons more responsive and amplify the magnetic signal from TMS to reach deeper brain tissue, aiding recovery. The finding offers new opportunities for treating neurological disorders. 

From impossible to possible

The research answers a key question in nanomedicine – whether it is possible to enhance TMS by using nanoparticles that are non-invasively delivered into the brain. Leading figures in the field previously stated that it was almost impossible because of the blood-brain barrier. This physical barrier separates the brain from the rest of the body’s bloodstream.

However, the team of researchers overcame this by guiding the magnetic nanoparticles closer to the correct area with a large magnet near the head. 

Dr Gang Ruan, a corresponding author of the study, says: “We were able to overcome the blood-brain barrier and send enough nanoparticles into the brain to use in combination with TMS simulation to improve recovery from stroke. 

“TMS devices are already used for the clinical treatment of neurological disorders but have severe limitations in terms of stimulation strength and depths of the brain they can penetrate. 

“By non-invasively putting magnetic nanoparticles into the brain, we can amplify and enhance the TMS stimulation effects on neurons, making the treatment more effective,” Dr Ruan adds.

“Showing it is possible to use nanoparticles in this way paves the way for medical applications of nanoparticles for other neurological disorders.”

Crossing barriers 

The iron oxide nanoparticles used in the study are already prescribed to treat iron deficiency as they are non-toxic and biodegradable. The team also modified the nanoparticles by coating them with various non-toxic substances. 

Dr Ruan says: “The coating causes the nanoparticles to stick to the blood-brain barrier, increasing their chances of passing through it. Without this coating, the particles just bounce back from the barrier instead of crossing it.

“The modifications of the iron oxide particles also ensure that the nanoparticles can stick to the neurons and increase their responsiveness to TMS stimulation.”

The safety of using the modified nanoparticles needs to be assessed in clinical trials but has the potential to be used in combination with TMS, and other methods such as brain imaging, to gain more insight into how the brain works and improve the treatment of neurological disorders. 

“Many scientists still think it is impossible to non-invasively send enough nanoparticles into the brain to affect brain function. Yet we have shown that it is possible,” says Dr Ruan.

“We combined the expertise on our team in four different disciplines, materials science, biophysics, neuroscience, and medical science, to push the boundaries of our knowledge and challenge what is currently thought in the field.”

Here’s a link to and a citation for the paper,

Enhancing non-invasive brain stimulation with non-invasively delivered nanoparticles for improving stroke recovery by Y. Hong, J. Wang, J. Li, Z. Xu, X. Yang, M. Bai, P. Gong, Y. Xi, X. Zhang, P. Xu, X. Chen, R. Li, X. Liu, G. Ruan, G. Xua. Materials Today Chemistry Volume 26, December 2022, 101104 DOI: https://doi.org/10.1016/j.mtchem.2022.101104 First available online: 19 August 2022

This paper is behind a paywall.

As promised, here are the links to the other posts about nasal sprays and nanoparticles:

One final note, “Xi’an Jiaotong-Liverpool University (XJTLU) is an international university formed in partnership between the University of Liverpool and Xi’an Jiaotong University in China. Find out more about XJTLU

Locusts inspire new aerosol-based nanoparticle drug delivery system

Getting medication directly to the brain is a worldwide medical research goal and it seems that a team of scientists at the Washington University at St. Louis (WUSTL) has taken a step forward to accomplishing the goal. From an April 12, 2017 news item on ScienceDaily,

Delivering life-saving drugs directly to the brain in a safe and effective way is a challenge for medical providers. One key reason: the blood-brain barrier, which protects the brain from tissue-specific drug delivery. Methods such as an injection or a pill aren’t as precise or immediate as doctors might prefer, and ensuring delivery right to the brain often requires invasive, risky techniques.

A team of engineers from Washington University in St. Louis has developed a new nanoparticle generation-delivery method that could someday vastly improve drug delivery to the brain, making it as simple as a sniff.

“This would be a nanoparticle nasal spray, and the delivery system could allow a therapeutic dose of medicine to reach the brain within 30 minutes to one hour,” said Ramesh Raliya, research scientist at the School of Engineering & Applied Science.

Caption: Engineers at Washington University have discovered a new technique that could change drug delivery to the brain. They were able to apply a nanoparticle aerosol spray to the antenna of locusts, then track the nanoparticles as they traveled through the olfactory nerves, crossed the blood-brain barrier and accumulated in the brain. This new, non-invasive approach could someday make drug delivery as simple as a sniff for patients with brain injuries or tumors.

Credit: Washington University in St. Louis

An April 12, 2017 WUSTL news release by Erika Ebsworth-Goold (also on EurekAlert), which originated the news item, describes the work in more detail,

“The blood-brain barrier protects the brain from foreign substances in the blood that may injure the brain,” Raliya said. “But when we need to deliver something there, getting through that barrier is difficult and invasive. Our non-invasive technique can deliver drugs via nanoparticles, so there’s less risk and better response times.”

The novel approach is based on aerosol science and engineering principles that allow the generation of monodisperse nanoparticles, which can deposit on upper regions of the nasal cavity via diffusion. Working with Assistant Vice Chancellor Pratim Biswas, chair of the Department of Energy, Environmental & Chemical Engineering and the Lucy & Stanley Lopata Professor, Raliya developed an aerosol consisting of gold nanoparticles of controlled size, shape and surface charge. The nanoparticles were tagged with fluorescent markers, allowing the researchers to track their movement.

Next, Raliya and biomedical engineering postdoctoral fellow Debajit Saha exposed locusts’ antennae to the aerosol, and observed the nanoparticles travel from the antennas up through the olfactory nerves. Due to their tiny size, the nanoparticles passed through the brain-blood barrier, reaching the brain and suffusing it in a matter of minutes.

The team tested the concept in locusts because the blood-brain barriers in the insects and humans have anatomical similarities, and the researchers consider going through the nasal regions to neural pathways as the optimal way to access the brain.

“The shortest and possibly the easiest path to the brain is through your nose,” said Barani Raman, associate professor of biomedical engineering. “Your nose, the olfactory bulb and then olfactory cortex: two relays and you’ve reached the cortex. The same is true for invertebrate olfactory circuitry, although the latter is a relatively simpler system, with supraesophageal ganglion instead of an olfactory bulb and cortex.”

To determine whether or not the foreign nanoparticles disrupted normal brain function, Saha examined the physiological response of olfactory neurons in the locusts before and after the nanoparticle delivery. Several hours after the nanoparticle uptake, no noticeable change in the electrophysiological responses was detected.

“This is only a beginning of a cool set of studies that can be performed to make nanoparticle-based drug delivery approaches more principled,” Raman said.

The next phase of research involves fusing the gold nanoparticles with various medicines, and using ultrasound to target a more precise dose to specific areas of the brain, which would be especially beneficial in brain-tumor cases.

“We want to drug target delivery within the brain using this non-invasive approach,” Raliya said.  “In the case of a brain tumor, we hope to use focused ultrasound so we can guide the particles to collect at that particular point.”

Here’s a link to and a citation for the paper,

Non-invasive aerosol delivery and transport of gold nanoparticles to the brain by Ramesh Raliya, Debajit Saha, Tandeep S. Chadha, Baranidharan Raman, & Pratim Biswas. Scientific Reports 7, Article number: 44718 (2017) doi:10.1038/srep44718 Published online: 16 March 2017

This paper is open access.

I featured another team working on delivering drugs directly to the brain via the olfactory system, except their nanoparticles were gelatin and they were testing stroke medication on rats, in my Sept. 24, 2014 posting.