Improved efficacy of Acetyl-L-Carnitine through nanoparticle delivery: a novel strategy against neuroinflammation and cerebral aging

Nanoparticles (NPs) represent the main products of nanotechnologies applied to medicine as an effective tool for drug delivery to specific body areas difficult to reach. Among these, the central nervous system (CNS) is one of the primary targets of NPs. Acetyl-L-carnitine (ALC) is a therapeutic adjuvant in patients suffering from different common neurological conditions. Although ALC is already capable to reach the brain, therapy with this supplement requires repeated administration over time at high doses to maintain constant levels. For these reasons, in our laboratory, a nanoparticle formulation of ALC (ALC-NP) has been synthetized using the Planetary Ball Milling, an innovative mechanical method which through the rotation and impact of raw powder causes the particles to be crushed to the nanometric size. The aim of this research is to highlight the advantages of ALC-NP over the bulk (non-nanoparticle) formulation on cultured nerve cells, with the goal of using significantly lower concentrations of ALC NP while maintaining the same therapeutic effect. Focus has been placed on specific inflammatory markers such as the alarmin S100B, that has been related to dementia or cerebral aging, and described as able to activate inflammatory pathways, as the NF- κB complex involved in the cytokine release. Its effect in the interference with the NF-κB pathway was evaluated by studying the ability to inhibit p65 phosphorylation, a NF-κB mediator, in TNF-α- stimulated cells. Finally, the effect on Nerve Growth Factor (NGF) production, a neurotropic protein crucial for neuron growth, differentiation and survival, and decreased in cerebral aging processes was considered. The results obtained showed an excellent activity of ALC-NP at much lower concentrations than the bulk form, suggesting that it may represent a promising strategy to enhance neuroprotective therapies, paving the way for more effective interventions in neurodegenerative and age-related brain disorders.