Blood-brain barrier models and their relevance for a successful development of CNS drug delivery systems: a review

Abstract

During the research and development of new drugs directed at the central nervous system, there is a considerable attrition rate caused by their hampered access to the brain by the blood-brain barrier. Throughout the years, several in vitro models have been developed in an attempt to mimic critical functionalities of the blood-brain barrier and reliably predict the permeability of drug candidates. However, the current challenge lies in developing a model that retains fundamental blood-brain barrier characteristics and simultaneously remains compatible with the high throughput demands of pharmaceutical industries. This review firstly describes the roles of all elements of the neurovascular unit and their influence on drug brain penetration. In vitro models, including non-cell based and cell-based models, and in vivo models are herein presented, with a particular emphasis on their methodological aspects. Lastly, their contribution to the improvement of brain drug delivery strategies and drug transport across the blood-brain barrier is also discussed.

Keywords: 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP (PubChem CID: 91636); Adenosine 3',5'-cyclic monophosphate (PubChem CID: 6076); Brain uptake; CNS drugs; Cell culture; Dodecane (PubChem CID: 8182); Drug discovery and development; Fluorescein isothiocyanate (PubChem CID: 18730); Hydrocortisone (PubChem CID: 5754); In vitro; In vivo; Inulin(PubChem CID: 18772499); Neurovascular unit; PAMPA; Permeability screening; Propranolol (PubChem CID: 4946); Sodium fluorescein (PubChem CID: 9885981); Sucrose (PubChem CID: 5988); Targeted drug delivery; Vinblastine (PubChem CID: 13342).