An In Vitro Evaluation of the Potential Neuroprotective Effects of Intranasal Lipid Nanoparticles Containing Astaxanthin Obtained from Different Sources: Comparative Studies

Abstract

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.

Dopamine- and Grape-Seed-Extract-Loaded Solid Lipid Nanoparticles: Interaction Studies between Particles and Differentiated SH-SY5Y Neuronal Cell Model of Parkinson’s Disease

“…In this study, we focused on the in vitro effects of DA/GSE-SLN administration by exploiting the advantage of differentiated SH-SY5Y cells both as promising models for developing therapies for PD and for testing SLNs [38][39][40]; the same study was previously conducted on undifferentiated SH-SY5Y cells [32]. The SLNs tested here are highly performing transport systems exploited by the pharmaceutical research for their ability to efficiently cross the BBB when the particle size is in the range of 200-500 nm, so they have an increased blood circulation time and the drug is in contact with the BBB for the maximum time.…”

Recent Advances in Intranasal Administration for Brain-Targeting Delivery: A Comprehensive Review of Lipid-Based Nanoparticles and Stimuli-Responsive Gel Formulations

“… [ 85 ] Astaxanthin (neuronal disease) Precirol ATO 5, vitamin E, Tween 80, SDC, BAC, and glycerin PS 97.610 nm, PDI 0.294, ZP −23.3 mV, and EE 98% The NLC formulation presented a greater neuroprotective effect than the SLN type. [ 86 ] Abbreviations : DTE, Drug-Targeting Efficiency; DTP, Drug Transport Percentage; EE, Encapsulation Efficiency; in, Intranasal Administration; IV, Intravenous Injection; PDI, Polydispersity Index; PO, Oral Administration; PS, Particle Size; ZP, Zeta Potential; indications; AD, Alzheimer’s disease; GAD, generalised anxiety disorder; GBM, glioblastoma multiforme; HD, Huntington’s disease; PD Parkinson’s disease; SCZ, schizophrenia; Excipients; BAC, benzalkonium chloride; CL, cholesterol; DHDHDAB, dihexadecylmethylhydroxyethylammonium bromide; DOPC, dipalmitoylphosphatidylcholine; DOTAP, 1.2-Dioleoyl-3-trimethylammonium propane; DSPE, 1.2-distearoyl-sn-glycero-3-phosphoethanolamine; GMS, glycerol monostearate; LPC, lysophosphatidylcholine; PC, phosphatidylcholine; PEG, polyethene glycol; SDC, sodium deoxycholate. …”

Recent Advances in the Therapeutic Potential of Carotenoids in Preventing and Managing Metabolic Disorders

“…In rat models treated with CCl 4 , astaxanthin NPs prepared with lecithin ameliorated hepatic damage and decreased plasma biomarker levels such as aminotransferase and aspartate aminotransferase [ 170 ]. Against potential neurological disorders, NPs or nanostructured lipid carriers containing astaxanthin demonstrated protective effects against MPP + (an active metabolite that mimics Parkinson’s disease), ferric iron, and tert-butyl hydroperoxide in SH-SY5Y cells [ 171 ].…”