Researchers have come up with a new nano-invention that uses ultra-fine gold particles as therapeutic carriers to deliver lithium directly to the brain in the form of a nasal spray, which opens promising horizons for the treatment and prevention of psychiatric and neurodegenerative diseases such as bipolar disorder and Alzheimer’s disease.
Lithium has been used for decades to treat some psychological disorders, but its oral use is limited due to the narrow margin of therapeutic safety and side effects that may affect the kidneys and thyroid gland.
Hence, researchers sought to find a way to deliver it directly to the brain in low concentrations and without passing through the blood circulation, which reduces the possibility of side effects and maintains its effectiveness.
The study was conducted by researchers from the Catholic University in Italy and the Policlinico University Hospital Foundation in cooperation with the University of Salerno in Italy, and the results were published in the journal Advanced Materials on September 29. The invention was patented, and the Eurick Alert website wrote about it.
This approach targets a key enzyme known as glycogen synthase kinase-3 beta (GSK-3β), an enzyme that plays an essential role in many cellular processes and affects more than 100 proteins within the cell.
When this enzyme is overactive, disorders occur in important proteins, which contributes to the emergence of neurological and psychological diseases. Lithium is considered a strong inhibitor of this enzyme, but reaching the required therapeutic concentration in the brain through oral tablets requires high doses that exceed safe limits.
Therefore, the research team worked to deliver lithium directly to the brain via gold nanoparticles by administering it through the nasal route.
Lithium and access to the brain
“Gold nanoparticles are an ideal tool for this strategy, as they can be modified with glutathione, which facilitates their entry into cells and binds lithium ions,” says Dr. Antonio Bonerba from the Department of Chemistry and Biology at the University of Salerno, co-author of this study. “After entry, the particles decompose and release lithium into the cell, allowing effective therapeutic concentrations to be achieved at low doses.”
Dr. Roberto Piacentini from the Department of Neurosciences, Catholic University, and co-researcher in this study, explains: “Intranasal administration is an ideal route to directly reach the brain and avoid systemic distribution, which increases the safety of the device. Gold is also an inert and biosafe metal, and is excreted through the kidneys without accumulating in the brain upon repeated use.”
The technology was tested on mice with Alzheimer’s disease, where the treatment showed a noticeable improvement in memory and behavior, without significant side effects.
“We showed that administration of lithium-loaded gold nanoparticles for 5 days inhibits the enzyme glycogen synthase kinase 3 beta in the hippocampus, and that repeat treatment for 2 months led to a significant improvement in memory at the behavioral and molecular levels,” explains Dr. Giulia Poliati from the Department of Neurosciences, Catholic University, a researcher involved in the study.
Experiments also showed that this treatment regulates the activity of the targeted enzyme in the brain without an increase in lithium levels in the blood, even with long-term use, which confirms the safety of the new technology.
“These nanoparticles can be easily manufactured, which simplifies the production process and reduces the cost, paving the way for the commercialization of this product in the near future,” says Dr. Claudio Grassi from the Department of Neurosciences, Catholic University, co-investigator of this study.
Researchers believe that this technology may bring about a qualitative shift in the treatment of psychological and neurodegenerative diseases through more accurate and safe medications directed directly to the brain.