Abstract
Therapies targeting neurological conditions such as Alzheimer's or Parkinson's diseases are hampered by the presence of the blood-brain barrier (BBB). During the last decades, several approaches have been developed to overcome the BBB, such as the use of nanoparticles (NPs) based on biomaterials, or alternative methods to open the BBB. In this review, we briefly highlight these strategies and the most recent advances in this field. Limitations and advantages of each approach are discussed. Combination of several methods such as functionalized NPs targeting the receptor-mediated transcytosis system with the use of magnetic resonance imaging-guided focused ultrasound (FUS) might be a promising strategy to develop theranostic tools as well as to safely deliver therapeutic molecules, such as drugs, neurotrophic factors or antibodies within the brain parenchyma.
Highlights
Brain parenchymal cells are isolated from the rest of the body by several barriers protecting them from neurotoxic molecules, pathogens, and circulating blood cells (Abbott et al, 2010)
The first objective of this review is to summarize our current knowledge on the development of different approaches to overcome the blood-brain barrier (BBB) to deliver therapeutic agents to the central nervous system (CNS), as well as imaging agents to diagnose Neurodegenerative diseases (NDs)
Among the different approaches developed since several decades, the use of NPs has received a lot of attention to improve the CNS delivery of small molecules and of peptides, DNA, or neurotrophic factors such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) or glial derived neurotrophic factor (GDNF)
Summary
Brain parenchymal cells are isolated from the rest of the body by several barriers protecting them from neurotoxic molecules, pathogens, and circulating blood cells (Abbott et al, 2010). Encapsulation of therapeutic mol ecules into nanoparticles (NPs) based on biomaterials could be used to increase its half-life into the human body (Schroeder et al, 2000) These NPs can be modified and functionalized to target the BBB endothelial cells, promoting CNS delivery of the cargo. The first objective of this review is to summarize our current knowledge on the development of different approaches to overcome the BBB to deliver therapeutic agents to the CNS, as well as imaging agents to diagnose NDs. Particular attention will be focused on the use of some types of NPs (PBCA, PLGA, cyclodextrins) able to target the receptormediated transcytosis (RMT) or to be coupled with BBB opening methods
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