In Vitro Models of the Blood–Cerebrospinal Fluid Barrier and Their Applications in the Development and Research of (Neuro)Pharmaceuticals

Abstract

The pharmaceutical research sector has been facing the challenge of neurotherapeutics development and its inherited high-risk and high-failure-rate nature for decades. This hurdle is partly attributable to the presence of brain barriers, considered both as obstacles and opportunities for the entry of drug substances. The blood–cerebrospinal fluid (CSF) barrier (BCSFB), an under-studied brain barrier site compared to the blood–brain barrier (BBB), can be considered a potential therapeutic target to improve the delivery of CNS therapeutics and provide brain protection measures. Therefore, leveraging robust and authentic in vitro models of the BCSFB can diminish the time and effort spent on unproductive or redundant development activities by a preliminary assessment of the desired physiochemical behavior of an agent toward this barrier. To this end, the current review summarizes the efforts and progresses made to this research area with a notable focus on the attribution of these models and applied techniques to the pharmaceutical sector and the development of neuropharmacological therapeutics and diagnostics. A survey of available in vitro models, with their advantages and limitations and cell lines in hand will be provided, followed by highlighting the potential applications of such models in the (neuro)therapeutics discovery and development pipelines.

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

“…The reader is referred to the reviews for additional information. 17 , 31 , 33 , 213 , 226 – 231 The most representative works were analyzed and systematically reproduced in Tables 2 and 3 . Timeline of technology evolution with key excerpts is visualized in Figure 3 .…”

Advancements in the Application of Nanomedicine in Alzheimer’s Disease: A Therapeutic Perspective

“…By using the current in vitro BCFB models, preliminary mechanistic and transport experiments can be used to assess the efficiency of the design process and the rate of successful transport across this barrier. Protein receptors, solute carriers, and amino acid transporters are three key groups of possible transporters that could be targeted to facilitate medication delivery to the CNS across the BCFB [ 78 ].…”

“…The capacity of the polymeric NPs to traverse the BBB is constrained without surface changes. Although these NPs have a good rate of disintegration, the chronic nature of neurodegenerative illnesses and the requirement for repeated doses of the therapeutic substance could result in polymer accumulation that could have unwanted side effects [ 78 , 175 ].…”

The application of nanotechnology in treatment of Alzheimer’s disease

“…Hence, to enhance the delivery of drugs to the brain, it is necessary to gain a comprehension of the structural and functional features of the BBB ( Sharifzad et al, 2019 ; Alahmari, 2021 ). Two specialized barriers, the cerebrospinal fluid barrier (CSFB) and BBB distinguish the complex human CNS ( Pathan et al, 2009 ; Dabbagh et al, 2022 ). Both cognitive impairment and dementia are caused by cerebrovascular dysfunction, which may result in cerebral amyloid angiopathy in AD.…”