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用于中枢神经系统治疗药物递送的纳米技术进展。

Nanotechnological advances for the delivery of CNS therapeutics.

机构信息

School of Pharmacy, Temple University, Philadelphia, PA 19140, USA.

出版信息

Adv Drug Deliv Rev. 2012 May 15;64(7):686-700. doi: 10.1016/j.addr.2011.10.007. Epub 2011 Nov 7.

Abstract

Effective non-invasive treatment of neurological diseases is often limited by the poor access of therapeutic agents into the central nervous system (CNS). The majority of drugs and biotechnological agents do not readily permeate into brain parenchyma due to the presence of two anatomical and biochemical dynamic barriers: the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Therefore, one of the most significant challenges facing CNS drug development is the availability of effective brain targeting technology. Recent advances in nanotechnology have provided promising solutions to this challenge. Several nanocarriers ranging from the more established systems, e.g. polymeric nanoparticles, solid lipid nanoparticles, liposomes, micelles to the newer systems, e.g. dendrimers, nanogels, nanoemulsions and nanosuspensions have been studied for the delivery of CNS therapeutics. Many of these nanomedicines can be effectively transported across various in vitro and in vivo BBB models by endocytosis and/or transcytosis, and demonstrated early preclinical success for the management of CNS conditions such as brain tumors, HIV encephalopathy, Alzheimer's disease and acute ischemic stroke. Future development of CNS nanomedicines need to focus on increasing their drug-trafficking performance and specificity for brain tissue using novel targeting moieties, improving their BBB permeability and reducing their neurotoxicity.

摘要

有效的神经疾病非侵入性治疗方法常常受到治疗剂进入中枢神经系统(CNS)的不良途径的限制。由于存在两种解剖学和生化动态屏障:血脑屏障(BBB)和血脑脊液屏障(BCSFB),大多数药物和生物技术制剂不易渗透到脑实质中。因此,CNS 药物开发面临的最大挑战之一是需要具有有效的脑部靶向技术。纳米技术的最新进展为此挑战提供了有希望的解决方案。已经研究了几种纳米载体,包括更成熟的系统,例如聚合物纳米颗粒、固体脂质纳米颗粒、脂质体、胶束,以及更新的系统,例如树枝状大分子、纳米凝胶、纳米乳液和纳米混悬剂,用于 CNS 治疗剂的递送。其中许多纳米药物可以通过内吞作用和/或转胞吞作用有效地穿过各种体外和体内 BBB 模型,并在管理 CNS 疾病(如脑肿瘤、HIV 脑病、阿尔茨海默病和急性缺血性中风)方面取得了早期临床前成功。未来 CNS 纳米药物的开发需要专注于使用新型靶向基团提高其药物转运性能和对脑组织的特异性,提高其 BBB 通透性并降低其神经毒性。

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