Torres Joana, Pereira José Miguel, Marques-Oliveira Rita, Costa Inês, Gil-Martins Eva, Silva Renata, Remião Fernando, Peixoto Andreia Filipa, Sousa Lobo José Manuel, Silva Ana Catarina
UCIBIO, REQUIMTE, Laboratory of Pharmaceutical Technology/Centre of Research in Pharmaceutical Sciences, Faculty of Pharmacy, University of Porto, 4099-002 Porto, Portugal.
Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4099-002 Porto, Portugal.
Pharmaceutics. 2023 Mar 23;15(4):1035. doi: 10.3390/pharmaceutics15041035.
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 and pure astaxanthin (PA) from the fungi ) 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.
鼻内给药途径被认为是一种有前景的替代方法，可改善分子向大脑的直接转运，避免了穿越血脑屏障（BBB）的需求。在这一领域，脂质纳米颗粒，即固体脂质纳米颗粒（SLN）和纳米结构脂质载体（NLC）的应用，已被视为改善神经退行性疾病治疗的一种有前景的策略。在本研究中，制备了含有从不同来源获得虾青素（藻类虾青素提取物（AE）和真菌纯虾青素（PA））的SLN和NLC的制剂用于鼻脑给药，并进行了比较体外实验以评估制剂与鼻（RPMI 2650）和神经元（SH-SY5Y）细胞的生物相容性。之后，使用不同的化学刺激物评估了制剂的抗氧化活性及其潜在的神经保护作用。最后，对显示出对神经元细胞化学诱导损伤具有最大神经保护作用的制剂评估了虾青素的细胞摄取情况。在生产当天，所有制剂均显示出粒径、高包封率（EE）、存在典型球形的纳米颗粒以及适合鼻脑给药的多分散指数（PDI）和zeta电位（ZP）。在室温下储存三个月后，表征参数未观察到显著变化，预示着良好的长期稳定性。此外，这些制剂在分化的SH-SY5Y和RPMI 2650细胞中浓度高达100 µg/mL时显示出安全性。关于神经保护研究，载有PA的SLN和NLC制剂显示出抵消某些神经退行性变机制（包括氧化应激）的能力。此外，与载有PA的SLN相比，载有PA的NLC对刺激物诱导的细胞毒性显示出更大的神经保护作用。相反，载有AE的SLN和NLC制剂未显示出显著的神经保护作用。尽管需要进一步研究来证实这些神经保护作用，但本研究结果表明，鼻内给予载有PA的NLC可能是改善神经退行性疾病治疗的一种有前景的替代方法。
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