BACKGROUND & AIMS:
:Alzheimer's disease (AD) is neurological disorder characterized by dementia which causes severe problems with behavior, thinking and memory. Systemic administration of therapeutics to the central nervous system (CNS) is usually associated with very low efficiency due to presence of blood brain barrier (BBB), which only allows permeation of few types of molecules from the circulation to the CNS. As an alternative, naturally amphiphilic micelles can be utilized to enhance targeted drug delivery to the brain. In this sense, lactoferrin (LF) was covalently attached to conjugated linoleic acid (CLA) via carbodiimide coupling reaction to form a new micellar nanoplatform with particle size of about 53 nm. Afterwards, fabricated micelles were further loaded once again with CLA to enhance its delivery to the CNS. In vitro drug release study revealed that CLA exhibited sustained release at pH 6.8, associated with good hemocompatibility without any remarkable in vivo toxicity in terms of liver and kidney functions. Moreover, in vivo studies showed that the fabricated micelles manifested enhanced in vivo biodistrbution in brain tissue due to the active targeting potential of LF. Additionally, drug-loaded LF-CLA micelles exhibited enhanced cognitive capabilities, reduced brain oxidative stress, inflammation, apoptosis and acetylcholine esterase activity, besides a decline in the deposition of amyloid β peptide1-42 in aluminum chloride Alzheimer's-induced animal model. CLA-based micelles could be a promising CNS actively targeted delivery system with a sophisticated potential to reduce AD symptoms.
背景与目标:
: 阿尔茨海默氏病 (AD) 是一种以痴呆为特征的神经系统疾病,会导致行为,思维和记忆方面的严重问题。由于存在血脑屏障 (BBB),对中枢神经系统 (CNS) 进行全身治疗通常效率很低,这仅允许从循环到CNS的少数类型分子渗透。作为替代方案,可以利用天然两亲胶束来增强靶向药物向大脑的递送。从这个意义上讲,乳铁蛋白 (LF) 通过碳二亚胺偶联反应与共轭亚油酸 (CLA) 共价连接,形成粒径约为53 nm的新胶束纳米胶束。之后,制造的胶束再次被进一步装载CLA,以增强其向CNS的递送。体外药物释放研究表明,CLA在pH 6.8下表现出持续释放,与良好的血液相容性相关,而在肝和肾功能方面没有任何显着的体内毒性。此外,体内研究表明,由于LF的主动靶向潜力,所制造的胶束在脑组织中表现出增强的体内生物分布。此外,载药的LF-CLA胶束表现出增强的认知能力,降低了脑氧化应激,炎症,凋亡和乙酰胆碱酯酶活性,此外,在氯化铝阿尔茨海默氏症诱导的动物模型中淀粉样 β peptide1-42的沉积减少。基于CLA的胶束可能是一种有前途的CNS主动靶向递送系统,具有减轻AD症状的复杂潜力。