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探索新型策略以实现治疗药物穿越血脑屏障的转运。

Evolving new-age strategies to transport therapeutics across the blood-brain-barrier.

机构信息

Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan 333031, India.

Birla Institute of Technology and Science, Pilani, Dubai Campus, United Arab Emirates.

出版信息

Int J Pharm. 2021 Apr 15;599:120351. doi: 10.1016/j.ijpharm.2021.120351. Epub 2021 Feb 2.

Abstract

A basic understanding of the blood-brain barrier (BBB) is essential for the novel advancements in targeting drugs specific to the brain. Neoplasm compromising the internal structure of BBB that results in impaired vasculature is called as blood tumor barrier (BTB). Besides, the BBB serves as a chief hindrance to the passage of a drug into the brain parenchyma. The small and hydrophilic drugs majorly display an absence of desired molecular characteristics required to cross the BBB. Furthermore, all classes of biologics have failed in the clinical trials of brain diseases over the past years since these biologics are large molecules that do not cross the BBB. Also, new strategies have been discovered that use the Trojan horse technology with the re-engineered biologics for BBB transport. Thus, this review delivers information about the different grades of tumors (I-IV) i.e. examples of BBB/BTB heterogenicity along with the different mechanisms for transporting the therapeutics into the brain tumors by crossing BBB. This review also provides insights into the emerging approaches of peptide delivery and the non-invasive and brain-specific molecular Trojan horse targeting technologies. Also, the several challenges in the clinical development of BBB penetrating IgG fusion protein have been discussed.

摘要

了解血脑屏障(BBB)的基础知识对于将药物靶向特定于大脑的新进展至关重要。破坏血管的肿瘤会破坏 BBB 的内部结构,从而导致血肿瘤屏障(BTB)的形成。此外,BBB 是药物进入脑实质的主要障碍。小分子和亲水性药物主要缺乏穿过 BBB 所需的理想分子特征。此外,过去几年,所有类别的生物制剂在治疗脑部疾病的临床试验中都失败了,因为这些生物制剂是大分子,无法穿过 BBB。还发现了新的策略,使用改良后的生物制剂的特洛伊木马技术进行 BBB 转运。因此,本综述提供了有关不同等级肿瘤(I-IV)的信息,即 BBB/BTB 异质性的例子,以及通过穿过 BBB 将治疗药物输送到脑肿瘤的不同机制。本综述还深入探讨了肽传递以及非侵入性和大脑特异性分子木马靶向技术的新兴方法。此外,还讨论了 BBB 穿透 IgG 融合蛋白临床开发中的几个挑战。

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