纳米医学:阿尔茨海默病药物靶向治疗的新前沿。

Kalyani Pathak, Mohammad Zaki Ahmad, Riya Saikia, Manash Pratim Pathak, Jon Jyoti Sahariah, Parimita Kalita, Aparoop Das, Md Ariful Islam, Pallab Pramanik, Dubom Tayeng, Basel A Abdel-Wahab
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引用次数: 0

摘要

阿尔茨海默病(AD)是一种影响老年人的常见神经退行性疾病,其特点是认知能力逐渐下降,最终导致痴呆。这篇综述探讨了血脑屏障 (BBB)、血-脑脊液屏障 (BCSFB) 和 p-glycoproteins 等解剖和生化屏障在向中枢神经系统 (CNS) 运送有效治疗药物以治疗 AD 方面所带来的挑战。本文概述了乙酰胆碱酯酶抑制剂(AChEIs)和NMDA(N-甲基-D-天冬氨酸)受体拮抗剂在传统AD治疗中的基本作用,并强调了它们在脑特异性递送方面的局限性。它深入探讨了阻碍药物向中枢神经系统转运的 BBB 和糖蛋白介导的外流机制的复杂性。综述进一步讨论了基于纳米药物的前沿策略,详细介绍了这些策略的组成和机制,这些策略能有效绕过 BBB 并增强药物在脑组织中的蓄积。传统疗法,即 AChEIs 和 NMDA 受体拮抗剂,显示出有限的疗效,并受制于不理想的脑穿透能力。纳米技术驱动的治疗给药系统的出现为增强中枢神经系统靶向性和生物利用度提供了前景广阔的策略,从而解决了传统疗法的不足之处。各种纳米药物,包括聚合物和金属纳米颗粒 (MNPs)、固体脂质纳米颗粒 (SLNs)、脂质体、胶束、树枝形分子、纳米乳液和碳纳米管,在递送 AChEIs、多酚、姜黄素和白藜芦醇等抗逆转录酶抑制剂方面的潜力已得到研究。这些纳米载体具有穿越 BBB 并将治疗有效载荷输送到大脑的能力,因此在有效治疗注意力缺失症和早期诊断方法方面具有巨大的潜力。值得注意的是,载入 AChEIs 的纳米载体在临床前研究中取得了令人鼓舞的成果,显示出更好的疗效和持续释放特性。这篇综述强调了采用创新给药方法克服注意力缺失症治疗障碍的紧迫性。基于纳米药物的解决方案为实现有效的中枢神经系统靶向、提高生物利用度和持续治疗效果提供了一条前景广阔的途径。随着正在进行的研究不断阐明中枢神经系统给药的复杂性,这些进展将为AD治疗和诊断带来巨大的变革潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Nanomedicine: A New Frontier in Alzheimer's Disease Drug Targeting.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting elderly individuals, characterized by progressive cognitive decline leading to dementia. This review examines the challenges posed by anatomical and biochemical barriers such as the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and p-glycoproteins in delivering effective therapeutic agents to the central nervous system (CNS) for AD treatment. This article outlines the fundamental role of acetylcholinesterase inhibitors (AChEIs) and NMDA(N-Methyl-D-Aspartate) receptor antagonists in conventional AD therapy and highlights their limitations in terms of brain-specific delivery. It delves into the intricacies of BBB and pglycoprotein-mediated efflux mechanisms that impede drug transport to the CNS. The review further discusses cutting-edge nanomedicine-based strategies, detailing their composition and mechanisms that enable effective bypassing of BBB and enhancing drug accumulation in brain tissues. Conventional therapies, namely AChEIs and NMDA receptor antagonists, have shown limited efficacy and are hindered by suboptimal brain penetration. The advent of nanotechnology-driven therapeutic delivery systems offers promising strategies to enhance CNS targeting and bioavailability, thereby addressing the shortcomings of conventional treatments. Various nanomedicines, encompassing polymeric and metallic nanoparticles (MNPs), solid lipid nanoparticles (SLNs), liposomes, micelles, dendrimers, nanoemulsions, and carbon nanotubes, have been investigated for their potential in delivering anti-AD agents like AChEIs, polyphenols, curcumin, and resveratrol. These nanocarriers exhibit the ability to traverse the BBB and deliver therapeutic payloads to the brain, thereby holding immense potential for effective AD treatment and early diagnostic approaches. Notably, nanocarriers loaded with AChEIs have shown promising results in preclinical studies, exhibiting improved therapeutic efficacy and sustained release profiles. This review underscores the urgency of innovative drug delivery approaches to overcome barriers in AD therapy. Nanomedicine-based solutions offer a promising avenue for achieving effective CNS targeting, enabling enhanced bioavailability and sustained therapeutic effects. As ongoing research continues to elucidate the complexities of CNS drug delivery, these advancements hold great potential for revolutionizing AD treatment and diagnosis.

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