Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Int J Nanomedicine. 2023 Mar 30;18:1631-1658. doi: 10.2147/IJN.S402447. eCollection 2023.
Astaxanthin (AST) is a second-generation antioxidant with anti-inflammatory and neuroprotective properties and could be a promising candidate for Alzheimer's disease (AD) therapy, but is shows poor oral bioavailability due to its high lipophilicity.
This study aimed to prepare and evaluate AST-loaded nanostructured lipid carriers (NLCs), for enhanced nose-to-brain drug delivery to improve its therapeutic efficacy in rat model of AD.
AST-NLCs were prepared using hot high-pressure homogenization technique, and processing parameters such as total lipid-to-drug ratio, solid lipid-to-liquid lipid ratio, and concentration of surfactant were optimized.
The optimized AST-NLCs had a mean particle size of 142.8 ± 5.02 nm, polydispersity index of 0.247 ± 0.016, zeta potential of -32.2 ± 7.88 mV, entrapment efficiency of 94.1 ± 2.46%, drug loading of 23.5 ± 1.48%, and spherical morphology as revealed by transmission electron microscopy. Differential scanning calorimetry showed that AST was molecularly dispersed in the NLC matrix in an amorphous state, whereas Fourier transform infrared spectroscopy indicated that there is no interaction between AST and lipids. AST displayed a biphasic release pattern from NLCs; an initial burst release followed by sustained release for 24 h. AST-NLCs were stable at 4-8 ±2°C for six months. Intranasal treatment of AD-like rats with the optimized AST-NLCs significantly decreased oxidative stress, amyloidogenic pathway, neuroinflammation and apoptosis, and significantly improved the cholinergic neurotransmission compared to AST-solution. This was observed by the significant decline in the levels of malondialdehyde, nuclear factor-kappa B, amyloid beta (Aβ), caspase-3, acetylcholinesterase, and β-site amyloid precursor protein cleaving enzyme-1 expression, and significant increase in the contents of acetylcholine and glutathione after treatment with AST-NLCs.
NLCs enhanced the intranasal delivery of AST and significantly improved its therapeutic properties.
虾青素（AST）是一种具有抗炎和神经保护作用的第二代抗氧化剂，可能是治疗阿尔茨海默病（AD）的有前途的候选药物，但由于其高亲脂性，口服生物利用度较差。
本研究旨在制备和评价载虾青素的纳米结构脂质载体（NLC），以增强鼻内递药，提高其在 AD 大鼠模型中的治疗效果。
采用高压均质热法制备 AST-NLC，并优化总脂质与药物比、固体脂质与液体脂质比、表面活性剂浓度等工艺参数。
优化的 AST-NLC 平均粒径为 142.8±5.02nm，多分散指数为 0.247±0.016，Zeta 电位为-32.2±7.88mV，包封率为 94.1±2.46%，载药量为 23.5±1.48%，透射电子显微镜显示为球形形态。差示扫描量热法显示 AST 以无定形状态分子分散在 NLC 基质中，而傅里叶变换红外光谱表明 AST 与脂质之间没有相互作用。AST 从 NLC 中呈两相释放模式；初始突释后持续释放 24 小时。AST-NLC 在 4-8±2°C 下稳定六个月。与 AST 溶液相比，AD 样大鼠经鼻内给予优化的 AST-NLC 可显著降低氧化应激、淀粉样蛋白形成途径、神经炎症和细胞凋亡，并显著改善胆碱能神经传递。这表现为 MDA、核因子-κB、淀粉样β（Aβ）、caspase-3、乙酰胆碱酯酶和β-位淀粉样前体蛋白裂解酶-1 表达水平显著下降，以及乙酰胆碱和谷胱甘肽含量显著增加。
NLC 增强了 AST 的鼻内递送，并显著改善了其治疗特性。
