Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
J Control Release. 2018 Dec 10;291:37-64. doi: 10.1016/j.jconrel.2018.10.004. Epub 2018 Oct 9.
Most of the potential therapeutic agents capable to modulate the pathophysiology or treat the neurological disorders and brain tumors are useless in the current modern and advanced era of neuroscience due to the impeding action of biological barriers. Among various therapeutic strategies applied for translocation of drug delivery across the blood-brain barrier (BBB), nanoformulations set an excellent platform for brain targeting by overcoming the biological and chemical barriers and protecting drug from efflux to promote the optimum therapeutic drug concentration in brain parenchyma tissues. Nanocarriers are the most widely studied delivery vehicles for BBB translocation with the efficiency of selectively targeting or exploiting inherent biological molecules, receptors, carriers or mechanisms of the brain. Nearly all of the available drug delivery nanocarriers explored in recent years for brain therapeutics and theranostics are based on lipid or polymeric materials. Polymeric nanoparticles (NPs) and lipid based nanocarriers including liposomes, solid lipid NPs (SLNs) and micelles, etc. are under the direct focus of neuroscientists due to the promising attributes and vast applications in neurological disorders. Surface modification of nanovehicles with proper targeting moiety or coating with surfactants promotes the interaction with endothelial cells and passage of nanocarriers to the brain. This review comprehensively depicts challenges to the brain targeted drug delivery, mechanisms of drug transportation across the BBB, and potential contributions of endogenous cells as NPs delivery cells and novel targeting ligands decorated nanoformulations in imaging, treating and controlling neurological disorders.
大多数能够调节神经病理生理学或治疗神经紊乱和脑肿瘤的潜在治疗药物,由于生物屏障的阻碍作用,在当前现代先进的神经科学时代都变得无用。在用于药物传递穿过血脑屏障(BBB)的各种治疗策略中,纳米制剂通过克服生物和化学屏障并保护药物免受外排,为大脑靶向提供了一个极好的平台,以促进脑实质组织中最佳的治疗药物浓度。纳米载体是用于 BBB 转运的最广泛研究的药物传递载体,具有选择性靶向或利用大脑固有生物分子、受体、载体或机制的效率。近年来,几乎所有用于脑治疗和治疗的可用药物递送纳米载体都基于脂质或聚合物材料。由于其有希望的特性和在神经紊乱中的广泛应用,聚合物纳米颗粒(NPs)和基于脂质的纳米载体,包括脂质体、固体脂质 NPs(SLNs)和胶束等,受到神经科学家的直接关注。通过适当的靶向部分对纳米载体进行表面修饰或用表面活性剂进行涂层,可促进与内皮细胞的相互作用和纳米载体向大脑的传递。这篇综述全面描述了针对大脑的药物输送的挑战、药物穿过 BBB 的运输机制,以及内源性细胞作为 NPs 输送细胞的潜在贡献,以及新型靶向配体修饰的纳米制剂在成像、治疗和控制神经紊乱方面的作用。