Reproducibility in biological models of the blood-brain barrier

In the past decade, the importance of quality and reproducibility within research has been re-emphasized, consequently becoming a crucial part of scientific experiments. Their implementation into in vitro and in vivo biological experiments is challenging due to various parameters that can influence the final scientific outcome. In parallel to these activities, there is a huge scientific effort to improve today's medicines to make them safer and more efficient, and to cure untreatable diseases, such as many neurodegenerative diseases. Nanosized materials have been recognized as potential drug delivery systems in this arena due to their small size and surface properties, which enable the design and synthesis of safe and efficient delivery vehicles that might be able to cross the blood-brain barrier. However, the fundamental understanding behind their uptake mechanism and intracellular trafficking remains unknown. Simple and cost-effective in vitro blood-brain barrier models are widely used to address these questions. This paper aims to critically evaluate the current in vitro models using Transwell (TM) systems and to discuss alternative approaches towards more reproducible in vivo features.