Tekade Avinash, Susar Ram, Kulkarni Gajanan, Surwade Samiksha, Gaikwad Anil
Department of Pharmaceutics, Marathwada Mitra Mandal's College of Pharmacy, Thergaon (Kalewadi), Pune, 411033 (M.S.), India.
Curr Alzheimer Res. 2024;21(10):710-722. doi: 10.2174/0115672050288659240229080535.
Alzheimer's Disease (AD) is a long-term brain disorder that worsens over time. A cholinesterase inhibitor called Donepezil HCl (DNZ) is used to treat and control AD. Due to its failure to reach the appropriate concentration in the brain cells, its efficacy upon oral administration is limited, and thus investigation of alternative administration route is necessary.
The objective of this study was to develop donepezil HCl-loaded Nanostructured Lipid Carriers (NLCs) that can bypass the blood-brain barrier and thus be directly delivered to the brain through the nasal route. This method improves availability at the site of action, reduces the negative effects of oral medication, and ensures an expedited commencement of action.
High-pressure homogenization and ultrasonication were used to formulate NLCs. Glyceryl Monostearate (GMS) as a solid lipid, Tween 80 as a surfactant, and Poloxamer 407 as a cosurfactant were used. In this study, argan oil was employed as a liquid lipid as well as a penetration enhancer.
The chosen NLCs displayed a particle size of 137.34 ± 0.79 nm, a PDI of 0.365 ± 0.03, and a zeta potential of -10.4 mV. The selected formulation showed an entrapment efficiency of 84.05 ± 1.30% and a drug content of 77.02 ± 0.23%. The concentration of the drug in the brain after intravenous and intranasal administration of DNZ NLCs at 1 h was found to be 0.490 ± 0.007 and 4.287 ± 0.115, respectively. Thus, the concentration of DNZ achieved in the brain after intranasal administration of DNZ NLCs was approximately 9 times more than the concentration when administered by intravenous route.
The DNZ-loaded NLCs, when administered via nasal route, showed markedly improved drug availability in the brain, suggesting an efficient drug delivery strategy to treat Alzheimer's disease.
阿尔茨海默病（AD）是一种会随着时间推移而恶化的慢性脑部疾病。一种名为盐酸多奈哌齐（DNZ）的胆碱酯酶抑制剂被用于治疗和控制AD。由于其在脑细胞中无法达到合适的浓度，口服给药的疗效有限，因此有必要研究其他给药途径。
本研究的目的是开发载有盐酸多奈哌齐的纳米结构脂质载体（NLCs），其能够绕过血脑屏障，从而通过鼻腔途径直接递送至脑部。该方法可提高作用部位的药物可及性，减少口服药物的不良反应，并确保药物更快起效。
采用高压均质法和超声法制备NLCs。使用单硬脂酸甘油酯（GMS）作为固体脂质，吐温80作为表面活性剂，泊洛沙姆407作为助表面活性剂。在本研究中，阿甘油既用作液体脂质，也用作渗透促进剂。
所制备的NLCs粒径为137.34±0.79nm，多分散指数（PDI）为0.365±0.03，ζ电位为-10.4mV。所选制剂的包封率为84.05±1.30%，药物含量为77.02±0.23%。静脉注射和鼻腔给药1小时后，DNZ NLCs在脑中的药物浓度分别为0.490±0.007和4.287±0.115。因此，鼻腔给药后DNZ在脑中达到的浓度约为静脉给药时浓度 的9倍。
经鼻腔给药的载DNZ的NLCs在脑中显示出显著提高的药物可及性，提示这是一种治疗阿尔茨海默病的有效给药策略。
