Tag Archives: Gelatin nanoparticles for drug delivery after a stroke

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

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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.

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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“

Reversing Parkinson’s type symptoms in rats

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Indian scientists have developed a technique for delivering drugs that could reverse Parkinson-like symptoms according to an April 22, 2015 news item on Nanowerk (Note: A link has been removed),

As baby boomers age, the number of people diagnosed with Parkinson’s disease is expected to increase. Patients who develop this disease usually start experiencing symptoms around age 60 or older. Currently, there’s no cure, but scientists are reporting a novel approach that reversed Parkinson’s-like symptoms in rats.

Their results, published in the journal ACS Nano (“Trans-Blood Brain Barrier Delivery of Dopamine-Loaded Nanoparticles Reverses Functional Deficits in Parkinsonian Rats”), could one day lead to a new therapy for human patients.

An April 22, 2015 American Chemical Society press pac news release (also on EurekAlert), which originated the news item, describes the problem the researchers were solving (Note: Links have been removed),

Rajnish Kumar Chaturvedi, Kavita Seth, Kailash Chand Gupta and colleagues from the CSIR-Indian Institute of Toxicology Research note that among other issues, people with Parkinson’s lack dopamine in the brain. Dopamine is a chemical messenger that helps nerve cells communicate with each other and is involved in normal body movements. Reduced levels cause the shaking and mobility problems associated with Parkinson’s. Symptoms can be relieved in animal models of the disease by infusing the compound into their brains. But researchers haven’t yet figured out how to safely deliver dopamine directly to the human brain, which is protected by something called the blood-brain barrier that keeps out pathogens, as well as many medicines. Chaturvedi and Gupta’s team wanted to find a way to overcome this challenge.

The researchers packaged dopamine in biodegradable nanoparticles that have been used to deliver other therapeutic drugs to the brain. The resulting nanoparticles successfully crossed the blood-brain barrier in rats, released its dopamine payload over several days and reversed the rodents’ movement problems without causing side effects.

The authors acknowledge funding from the Indian Department of Science and Technology as Woman Scientist and Ramanna Fellow Grant, and the Council of Scientific and Industrial Research (India).

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

Trans-Blood Brain Barrier Delivery of Dopamine-Loaded Nanoparticles Reverses Functional Deficits in Parkinsonian Rats by Richa Pahuja, Kavita Seth, Anshi Shukla, Rajendra Kumar Shukla, Priyanka Bhatnagar, Lalit Kumar Singh Chauhan, Prem Narain Saxena, Jharna Arun, Bhushan Pradosh Chaudhari, Devendra Kumar Patel, Sheelendra Pratap Singh, Rakesh Shukla, Vinay Kumar Khanna, Pradeep Kumar, Rajnish Kumar Chaturvedi, and Kailash Chand Gupta. ACS Nano, Article ASAP DOI: 10.1021/nn506408v Publication Date (Web): March 31, 2015
Copyright © 2015 American Chemical Society

This paper is open access.

Another recent example of breaching the blood-brain barrier, coincidentally, in rats, can be found in my Dec. 24, 2014 titled: Gelatin nanoparticles for drug delivery after a stroke. Scientists are also trying to figure out the the blood-brain barrier operates in the first place as per this April 22, 2015 University of Pennsylvania news release on EurekAlert titled, Penn Vet, Montreal and McGill researchers show how blood-brain barrier is maintained (University of Pennsylvania School of Veterinary Medicine, University of Montreal or Université de Montréal, and McGill University). You can find out more about CSIR-Indian Institute of Toxicology Research here.