The intranasal route has been suggested as a promising alternative to improve the direct transport of molecules to the brain, avoiding the need to cross the blood–brain barrier (BBB). In this area, the use of lipid nanoparticles, namely solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has been highlighted as a promising strategy to improve the treatment of neurodegenerative diseases. In this work, formulations containing SLN and NLC that were loaded with astaxanthin that was obtained from different sources (astaxanthin extract (AE) from the algae Haematococcus pluvialis and pure astaxanthin (PA) from the fungi Blakeslea trispora) were prepared for nose-to-brain administration, and comparative in vitro experiments were performed to evaluate the biocompatibility of the formulations with nasal (RPMI 2650) and neuronal (SH-SY5Y) cells. Afterwards, the antioxidant activity of the formulations was evaluated for its potential neuroprotective effects, using different chemical aggressors. Finally, the cellular uptake of the astaxanthin was evaluated for the formulations that showed the greatest neuroprotection of the neuronal cells against chemical-induced damage. On the production day, all the formulations showed a particle size, a high encapsulation efficiency (EE), the presence of nanoparticles with a typical spherical shape, and a polydispersity index (PDI) and zeta potential (ZP) that are suitable for nose-to-brain administration. After three months of storage at room temperature, no significant changes were observed in the characterization parameters, predicting a good long-term stability. Furthermore, these formulations were shown to be safe with concentrations of up to 100 µg/mL in differentiated SH-SY5Y and RPMI 2650 cells. Regarding neuroprotection studies, the PA-loaded SLN and NLC formulations showed an ability to counteract some mechanisms of neurodegeneration, including oxidative stress. Moreover, when compared with the PA-loaded SLN, the PA-loaded NLC showed greater neuroprotective effects against the cytotoxicity induced by aggressors. In contrast, the AE-loaded SLN and NLC formulations showed no significant neuroprotective effects. Although further studies are needed to confirm these neuroprotective effects, the results of this study suggest that the intranasal administration of PA-loaded NLC may be a promising alternative to improve the treatment of neurodegenerative diseases.

The intranasal route has been suggested as a promising alternative to improve drug delivery to the central nervous system, as it can transport drugs from the nose directly to the brain, avoiding the need to cross the blood-brain barrier and, therefore, can represent an effective strategy in the treatment of neurodegenerative diseases. Natural compounds, existent in marine microorganisms, can be used in the management of neurodegenerative diseases due to their remarkable antioxidant activity that reduces the oxidative stress associated with the development of these diseases. The objective of this work was to prepare solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for nose-to-brain delivery loaded with 1000 µg/mL of two natural antioxidants, in particular antioxidant extract and pure antioxidant. On the day of the production, all formulations had a particle size, polydispersity index and zeta potential suitable for nose-to-brain administration. In addition, all formulations showed high encapsulation efficiency of the tested natural antioxidants. Six months after storage at 20.0 ± 0.5 °C, in the case of SLN and NLC with antioxidant extract, and one month after storage, in the case of SLN and NLC with pure antioxidant, the characterization parameters underwent only slight changes. Biocompatibility studies in human neuronal cells SH-SY5Y, showed that the developed formulations are safe at least at concentrations up to 100 µg/mL. The results of this study highlighted the potential of using lipid nanoparticles loaded with natural antioxidants in the management of neurodegenerative diseases, although more experiments are needed to confirm this evidence.