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用于靶向药物递送的纳米系统:克服血脑屏障以用于神经退行性疾病和癌症治疗的创新和挑战。

Nanosystems for targeted drug Delivery: Innovations and challenges in overcoming the Blood-Brain barrier for neurodegenerative disease and cancer therapy.

机构信息

Department of Nanobiotechnology, Faculty of Biological Science, Tarbiat Modares University, 14115-154, Tehran, Iran.

Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600 077, India.

出版信息

Int J Pharm. 2024 Dec 5;666:124800. doi: 10.1016/j.ijpharm.2024.124800. Epub 2024 Oct 5.

DOI:10.1016/j.ijpharm.2024.124800
PMID:39374818
Abstract

The evolution of sophisticated nanosystems has revolutionized biomedicine, notably in treating neurodegenerative diseases and cancer. These systems show potential in delivering medication precisely to affected tissues, improving treatment effectiveness while minimizing side effects. Nevertheless, a major hurdle in targeted drug delivery is breaching the blood-brain barrier (BBB), a selective shield separating the bloodstream from the brain and spinal cord. The tight junctions between endothelial cells in brain capillaries create a formidable physical barrier, alongside efflux transporters that expel harmful molecules. This presents a notable challenge for brain drug delivery. Nanosystems present distinct advantages in overcoming BBB challenges, offering enhanced drug efficacy, reduced side effects, improved stability, and controlled release. Despite their promise, challenges persist, such as the BBB's regional variability hindering uniform drug distribution. Efflux transporters can also limit therapeutic agent efficacy, while nanosystem toxicity necessitates rigorous safety evaluations. Understanding the long-term impact of nanomaterials on the brain remains crucial. Additionally, addressing nanosystem scalability, cost-effectiveness, and safety profiles is vital for widespread clinical implementation. This review delves into the advancements and obstacles of advanced nanosystems in targeted drug delivery for neurodegenerative diseases and cancer therapy, with a focus on overcoming the BBB.

摘要

复杂纳米系统的发展彻底改变了生物医药领域,特别是在治疗神经退行性疾病和癌症方面。这些系统在将药物精确递送到病变组织方面显示出了潜力,提高了治疗效果,同时最大限度地减少了副作用。然而,靶向药物输送的一个主要障碍是突破血脑屏障(BBB),BBB 是一种选择性屏障,将血液与大脑和脊髓隔开。脑毛细血管内皮细胞之间的紧密连接构成了一个强大的物理屏障,同时外排转运蛋白会将有害物质排出。这对脑部药物输送来说是一个显著的挑战。纳米系统在克服 BBB 挑战方面具有明显的优势,能够提高药物疗效、减少副作用、增强稳定性和控制释放。尽管它们有很大的应用前景,但仍然存在一些挑战,例如 BBB 的区域变异性会阻碍药物的均匀分布。外排转运蛋白也会限制治疗剂的疗效,而纳米系统的毒性需要进行严格的安全性评估。了解纳米材料对大脑的长期影响仍然至关重要。此外,解决纳米系统的可扩展性、成本效益和安全性问题对于广泛的临床应用至关重要。本综述深入探讨了先进的纳米系统在神经退行性疾病和癌症治疗中的靶向药物输送方面的进展和障碍,重点是克服 BBB。

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