Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Daru. 2018 Dec;26(2):165-177. doi: 10.1007/s40199-018-0221-5. Epub 2018 Nov 1.
Nicotinamide is considered to be effective in halting the Alzheimer's disease progression. The body could absorb a limited amount of nicotinamide at a time, requiring multiple doses through a day. To overcome such an obstacle which reduces the patient compliance, a sustained/controlled delivery system could be useful.
Nicotinamide loaded solid lipid nanoparticles (SLN) were prepared and functionalized with polysorbate 80 (S80), phosphatidylserine (PS) or phosphatidic acid (PA). The acquired particles were characterized and evaluated in respect of their cytotoxicity, biodistribution, and in vivo effectiveness through the different routes of administration.
The optimum sizes of 112 ± 1.6 nm, 124 ± 0.8 nm, and 137 ± 1.05 nm were acquired for S80-, PS-, and PA-functionalized SLNs, respectively. The in vitro cytotoxicity on SH-SY5Y cell line showed the safety of formulations except for S80-functionalized SLNs. Biodistribution study of SLNs has proved the benefits of functionalization in improving the brain delivery. The results of spatial and memory test, i.e. Morris water maze, and also histopathology and biochemical tests demonstrated the effectiveness of i.p. injection of PS -functionalized SLNs in improving the cognition, preserving the neuronal cells and reducing tau hyperphosphorylation in a rat model of Alzheimer's disease.
The acquired PS-functionalized SLN could be a potential brain delivery system. Loaded with nicotinamide, an HDAC inhibitor, it could ameliorate the cognition impairment of rats more effectively than the conventional administration of nicotinamide, i.e. oral, in the early stage of Alzheimer's disease. Graphical abstract ᅟ.
烟酰胺被认为可以有效阻止阿尔茨海默病的进展。人体一次只能吸收有限量的烟酰胺，因此需要一天多次服用。为了克服这种降低患者依从性的障碍，可以使用持续/控制释放系统。
制备并功能化了烟酰胺负载的固体脂质纳米粒（SLN），用聚山梨酯 80（S80）、磷脂酰丝氨酸（PS）或磷脂酸（PA）进行功能化。对获得的颗粒进行了表征，并通过不同的给药途径评估了其细胞毒性、生物分布和体内效果。
分别获得了 S80、PS 和 PA 功能化 SLN 的最佳粒径为 112±1.6nm、124±0.8nm 和 137±1.05nm。在 SH-SY5Y 细胞系上的体外细胞毒性研究表明，除 S80 功能化 SLN 外，这些制剂都是安全的。SLN 的生物分布研究证明了功能化在改善脑内递药方面的优势。空间和记忆测试（即 Morris 水迷宫）以及组织病理学和生化测试的结果表明，PS 功能化 SLN 通过腹腔注射给药，可改善认知，保护神经元细胞，并减少阿尔茨海默病大鼠模型中 tau 过度磷酸化。
所获得的 PS 功能化 SLN 可能是一种有潜力的脑内递药系统。负载组蛋白去乙酰化酶抑制剂烟酰胺后，它可以比常规的烟酰胺口服给药更有效地改善阿尔茨海默病早期大鼠的认知障碍。
