Nasal Spray Of Gold Nanoparticles Delivers Lithium Directly To The Brain

In nan shape of a 'nasal spray', mini golden particles enactment arsenic carriers, delivering a curen straight to nan brain: developed by scientists astatine nan Università Cattolica Rome campus/Fondazione Policlinico Universitario A. Gemelli IRCCS, a caller nanotechnological instrumentality for nan curen and prevention of neuropsychiatric and neurodegenerative diseases. These are lithium-loaded golden nanoparticles (lithium is already successful objective usage for manic-depressive syndrome, but successful oral formulation, not free from broadside effects) to combat neuropsychiatric diseases specified arsenic bipolar disorder, neurodegenerative diseases specified arsenic Alzheimer's disease, and encephalon infections specified arsenic those caused by Herpes Simplex Virus type 1, which respective caller studies person linked to an accrued consequence of neurological diseases.

Published successful nan diary Advanced Materials and already patented, nan thought is nan consequence of a study conducted by researchers from Università Cattolica Medical School and Fondazione Policlinico Universitario Agostino Gemelli IRCCS, successful collaboration pinch nan University of Salerno.

The investigation team, led by Roberto Piacentini, subordinate professor of Physiology astatine Università Cattolica - Fondazione Policlinico Universitario A. Gemelli IRCCS, Antonio Buonerba, subordinate professor of inorganic chemistry astatine nan University of Salerno, and Alfonso Grassi, afloat professor of inorganic chemistry astatine nan University of Salerno, and Claudio Grassi, Professor of Physiology and Director of nan Department of Neuroscience astatine nan Università Cattolica/Fondazione Policlinico Universitario Agostino Gemelli IRCCS, demonstrated that it is imaginable to straight inhibit nan activity of an enzyme that plays a cardinal domiciled successful nan improvement of these diseases (glycogen synthase kinase-3 beta, GSK-3β) straight successful nan brain, by utilizing lithium delivered by intranasally administered golden nanoparticles.

This innovative therapeutic approach, which has sewage a patent successful Italy and overseas by nan researchers' affiliated institutions, achieves nan aforesaid effects arsenic orally administered lithium but utilizing importantly little concentrations of this ion and targeting it specifically to nan brain, thereby reducing nan consequence of broadside effects.

In nan study, nan researchers demonstrated nan effectiveness of this caller nanotechnological instrumentality successful inhibiting nan activity of nan GSK-3β enzyme successful nan hippocampus and restoring representation already compromised successful an experimental exemplary of Alzheimer's disease, without adverse events successful nan treated animals.

The investigation was funded pinch an grant by nan Alzheimer's Association (USA) to Profs. Piacentini and Buonerba and nan support of nan Agostino Gemelli IRCCS University Hospital Foundation.

Studies are presently underway to verify different areas of exertion for this instrumentality and to complete its information appraisal successful bid to proceed quickly pinch its objective application.

Background

GSK-3β is an enzyme that is basal for galore cellular functions: it is estimated that much than 100 proteins are targeted by this kinase, which is simply a molecular instrumentality that attaches a chemic group (phosphate) to different molecules, truthful modifying their function. Abnormal activation of this enzyme tin truthful origin malfunctioning of nan target proteins and beforehand nan onset of various diseases. In nan lawsuit of neurodegenerative diseases, specified arsenic Alzheimer's disease, aliases neuropsychiatric disorders specified arsenic bipolar disorder, hyperactivation of nan GSK-3β enzyme is observed, which successful move involves cardinal proteins, specified arsenic tau protein, and aberrant activation of nan "Wnt/β-catenin" pathway, progressive successful nan introduction of various viruses, specified arsenic Herpes Simplex 1 and SARS-CoV-2. Controlling nan activation of this enzyme successful circumstantial areas of nan encephalon could truthful counteract nan onset of these diseases.

Lithium is simply a potent inhibitor of GSK-3β and is presently successful usage successful nan curen of neuropsychiatric disorders specified arsenic bipolar disorder. The concentrations of lithium needed to counteract nan molecular mechanisms responsible for neurodegenerative diseases aliases viral infections affecting nan cardinal nervous system are higher than those considered acceptable successful position of risk/benefit ratio, importantly limiting nan therapeutic applications of this drug.

Professor Piacentini explains: "Our situation was to create a instrumentality that would let america to utilization nan therapeutic imaginable of lithium without causing adverse effects and that could beryllium delivered successful a site-specific manner, avoiding systemic administration."

Professor Buonerba adds: "Gold nanoparticles are nan optimal instrumentality for this type of strategy. They tin beryllium functionalized pinch glutathione, which, connected nan 1 hand, promotes nan statement of aggregates that easy participate cells and, connected nan other, allows molecules aliases ions, specified arsenic lithium, to bind. Once nan nanoparticle aggregates participate nan cells, they are surgery down and nan lithium is released into nan cells, allowing effective therapeutic concentrations of this ion to beryllium obtained pinch debased doses of administration."

Professor Piacentini continues: "Furthermore, nan intranasal way is an elective way for straight targeting nan encephalon and bypassing nan systemic circulation, frankincense optimizing nan information of our nanodevice. Gold, an inert metallic that has already been proven to beryllium harmless successful biologic systems, is eliminated done renal excretion, limiting its accumulation successful nan encephalon pursuing repeated administrations complete time."

Professor Antonio Buonerba points out: "The versatility of this caller pharmaceutical vector is extraordinary. The nanoparticles developed tin beryllium loaded pinch different pharmacological progressive ingredients and are capable to evade biologic cellular defenses, allowing their targeted carrier to circumstantial physiological progressive sites."

"In this activity we person shown that 5 days of management of golden nanoparticles functionalized pinch glutathione and coated pinch lithium (called LiG-AuNPs) tin importantly inhibit nan activity of GSK-3β kinase successful nan hippocampus of mice, and that nan aforesaid curen repeated for 2 months leads to a important regression of nan representation shortage exhibited by a rodent exemplary of Alzheimer's disease, analyzed astatine nan behavioral and molecular levels", first writer Doctor Giulia Puliatti explains.

Towards caller curen possibilities

Professor Claudio Grassi emphasizes: "To date, lithium-based narcotics are wide utilized for nan curen of neuropsychiatric diseases, but unfortunately, they are not without important broadside effects. Taken orally successful tablet form, lithium reaches nan encephalon done nan bloodstream and truthful ends up exerting toxic effects connected different organs specified arsenic nan kidneys and thyroid. Achieving effective concentrations of lithium successful nervus cells done 'brain-targeted' management of debased doses of nan ion pinch nan assistance of golden nanoparticles is truthful an important invention for nan improvement of caller and safer ways of treating patients. We judge that our nanotechnological instrumentality tin alteration nan improvement of caller therapeutic approaches not only for psychiatric disorders but besides for neurodegenerative and viral diseases successful which altered GSK-3β activity successful nan encephalon plays a cardinal role."

Professor Alfonso Grassi concludes: "Finally, our nanoparticles tin beryllium synthesized very easy and that simplifies nan accumulation process, keeping debased nan costs of manufacturing a merchandise that whitethorn beryllium launched connected nan pharmaceutical marketplace successful nan adjacent future."