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抗氧化剂的鼻-脑递送作为神经疾病治疗的潜在工具

Nose-to-Brain Delivery of Antioxidants as a Potential Tool for the Therapy of Neurological Diseases.

作者信息

Bonferoni Maria Cristina, Rassu Giovanna, Gavini Elisabetta, Sorrenti Milena, Catenacci Laura, Giunchedi Paolo

机构信息

Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy.

Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy.

出版信息

Pharmaceutics. 2020 Dec 21;12(12):1246. doi: 10.3390/pharmaceutics12121246.

Abstract

Oxidative stress has a key role in the pathogenesis of neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases and can be an important cause of the damages in cerebral ischemia. Oxidative stress arises from high levels of reactive oxygen species (ROS). Consequently, on this rational base, antioxidants (many of natural origin) are proposed as potential drugs to prevent ROS noxious actions because they can protect the target tissues from the oxidative stress. However, the potential of antioxidants is limited, owing to the presence of the blood-brain barrier (BBB), which is difficult to cross with a consequent low bioavailability of the drug into the brain after systemic (intravenous, intraperitoneal, oral) administrations. One strategy to improve the delivery of antioxidants to the brain involves the use of the so-called nose-to-brain route, with the administration of the antioxidant in specific nasal formulations and its passage to the central nervous system (CNS) mainly through the olfactory nerve way. In the current literature, many examples show encouraging results in studies carried out in cell cultures and in animal models about the potential neuroprotective effects of antioxidants when administered through the nose. This review concerns the nose-to-brain route for the brain targeting of antioxidants as a potential tool for the therapy of neurological diseases.

摘要

氧化应激在神经退行性疾病(如阿尔茨海默病、帕金森病和亨廷顿病)的发病机制中起关键作用,并且可能是脑缺血损伤的一个重要原因。氧化应激源于高水平的活性氧(ROS)。因此,基于这一合理依据,抗氧化剂(许多是天然来源)被提议作为预防ROS有害作用的潜在药物,因为它们可以保护靶组织免受氧化应激的影响。然而,由于血脑屏障(BBB)的存在,抗氧化剂的潜力受到限制,血脑屏障难以跨越,导致药物经全身(静脉、腹腔、口服)给药后进入大脑的生物利用度较低。一种改善抗氧化剂向大脑递送的策略涉及使用所谓的鼻脑途径,即将抗氧化剂制成特定的鼻腔制剂给药,其主要通过嗅神经途径进入中枢神经系统(CNS)。在当前文献中,许多例子表明,在细胞培养和动物模型中进行的研究显示,通过鼻腔给药抗氧化剂具有潜在的神经保护作用,结果令人鼓舞。这篇综述关注抗氧化剂的鼻脑途径作为治疗神经疾病的潜在工具用于脑靶向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1e4/7766211/d1c5416c6986/pharmaceutics-12-01246-g001.jpg

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