UCIBIO, REQUIMTE, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
FP-ENAS/CEBIMED, Fernando Pessoa Energy, Environment and Health Research Unit/Biomedical Research Centre, Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal.
Eur J Pharm Biopharm. 2020 Apr;149:192-217. doi: 10.1016/j.ejpb.2020.01.005. Epub 2020 Jan 23.
The central nervous system (CNS) is vulnerable to pathologic processes that lead to the development of neurodegenerative disorders like Alzheimer's, Parkinson's and Huntington's diseases, Multiple sclerosis or Amyotrophic lateral sclerosis. These are chronic and progressive pathologies characterized by the loss of neurons and the formation of misfolded proteins. Additionally, neurodegenerative diseases are accompanied by a structural and functional dysfunction of the blood-brain barrier (BBB). Although serving as a protection for the CNS, the existence of physiological barriers, especially the BBB, limits the access of several therapeutic agents to the brain, constituting a major hindrance in neurotherapeutics advancement. In this regard, nanotechnology-based approaches have arisen as a promising strategy to not only improve drug targeting to the brain, but also to increase bioavailability. Lipid nanocarriers such as liposomes, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), microemulsions and nanoemulsions, have already proven their potential for enhancing brain transport, crossing more easily into the CNS and allowing the administration of medicines that could benefit the treatment of neurological pathologies. Given the socioeconomic impact of such conditions and the advent of nanotechnology that inevitably leads to more effective and superior therapeutics for their management, it is imperative to constantly update on the current knowledge of these topics. Herein, we provide insight on the BBB and the pathophysiology of the main neurodegenerative disorders. Moreover, this review seeks to highlight the several approaches that can be used to improve the delivery of therapeutic agents to the CNS, while also offering an extensive overview of the latest efforts regarding the use of lipid-based nanocarriers in the management of neurodegenerative diseases.
中枢神经系统(CNS)易受到导致神经退行性疾病(如阿尔茨海默病、帕金森病和亨廷顿病、多发性硬化症或肌萎缩性侧索硬化症)发展的病理过程的影响。这些是慢性和进行性的病理疾病,其特征是神经元丧失和错误折叠蛋白的形成。此外,神经退行性疾病伴随着血脑屏障(BBB)的结构和功能障碍。尽管中枢神经系统起到保护作用,但生理屏障的存在,特别是 BBB,限制了许多治疗剂进入大脑,这是神经治疗进展的主要障碍。在这方面,基于纳米技术的方法已成为一种很有前途的策略,不仅可以改善药物对大脑的靶向性,还可以提高生物利用度。脂质纳米载体,如脂质体、固体脂质纳米粒(SLN)、纳米结构脂质载体(NLC)、微乳液和纳米乳液,已经证明了它们在增强脑内转运、更容易进入中枢神经系统以及允许管理可能有益于治疗神经病理的药物方面的潜力。鉴于这些疾病的社会经济影响以及纳米技术的出现不可避免地导致了更有效和更优越的治疗方法,因此必须不断更新这些主题的最新知识。在此,我们提供了对 BBB 和主要神经退行性疾病的病理生理学的深入了解。此外,本综述旨在强调几种可用于改善治疗剂向 CNS 传递的方法,同时广泛概述了关于使用基于脂质的纳米载体管理神经退行性疾病的最新努力。