Evolution of blood–brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies

Abstract

Blood–brain barrier (BBB) strictly controls matter exchange between blood and brain, and severely limits brain penetration of systemically administered drugs, resulting in ineffective drug therapy of brain diseases. However, during the onset and progression of brain diseases, BBB alterations evolve inevitably. In this review, we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer's disease, Parkinson's disease, epilepsy, stroke, traumatic brain injury and brain tumor. The advances on optimization of small molecules for BBB crossing and non-systemic administration routes ( e . g ., intranasal treatment) for BBB bypassing are not included in this review.

Blood–Brain Barrier Disruption Mediated by FFA1 Receptor—Evidence Using Miniscope

“…Moreover, FFA1-selective agonists are still being considered as potential therapeutic agents for the treatment of metabolic disorders such as type 2 diabetes [57][58][59]. In addition, the transient increase in BBB permeability produced by FFA1 activation can facilitate access to the brain by other drugs which are administered concomitantly with DHA/n-3 PUFAs, or can be used as a potential tool to improve drug delivery to the brain [60,61].…”

Selective Sphingosine-1-phosphate Receptor 1 Modulator Attenuates Blood–brain Barrier Disruption Following Traumatic Brain Injury by Inhibiting Vesicular Transcytosis

“…Multiple secondary pathological processes occur after TBI, and BBB breakdown is considered to be one of the initial changes [33]. The BBB consists of speci c brain capillary ECs that are utilized for a highly specialized transport system [34], and the BBB regulates ion balance and nutrient transport and blocks the possibly detrimental particles that act as an interface between the CNS and peripheral circulatory system [35]. Disruption of the structure and function of the BBB disturbs neuronal functions and leads to neurological disruption, such as CBF alteration, water imbalance, cerebral metabolism imbalance, and the accumulation of in ammatory molecules [33].…”

Ginsenoside Rg1 ameliorates blood–brain barrier disruption and traumatic brain injury via attenuating macrophages derived exosomes miR-21 release

“…BBB regulates ionbalance, nutrient transport and blocks the possibly detrimental particles that act as an interface between the CNS and peripheral circulatory system 46 , 47 ; and it consists of specific brain capillary endothelial cells for highly specialized transport system 48 , 49 . Disruption of BBB and TJPs strictly disturb the neuronal functions and lead to neurological diseases 46 .…”