Influence factors on and potential strategies to amplify receptor-mediated nanodrug delivery across the blood–brain barrier

INTRODUCTION: A major challenge in treating central nervous system (CNS) disorders is to achieve adequate drug delivery across the blood-brain barrier (BBB). Receptor-mediated nanodrug delivery as a Trojan horse strategy has become an exciting approach. However, these nanodrugs do not accumulate significantly in the brain parenchyma, which greatly limits the therapeutic effect of drugs. Amplifying the efficiency of receptor-mediated nanodrug delivery across the BBB becomes the holy grail in the treatment of CNS disorders. AREAS COVERED: In this review, we tend to establish links between dynamic BBB and receptor-mediated nanodrug delivery, starting with the delivery processes across the BBB, describing factors affecting nanodrug delivery efficiency, and summarizing potential strategies that may amplify delivery efficiency. EXPERT OPINION: Receptor-mediated nanodrug delivery is a common approach to significantly enhance the efficiency of brain-targeting delivery. As BBB is constantly undergoing changes, it is essential to investigate the impact of diseases on the effectiveness of brain-targeting nanodrug delivery. More critically, there are several barriers to achieving brain-targeting nanodrug delivery in the five stages of receptor-mediated transcytosis (RMT), and the impacts can be conflicting, requiring intricate balance. Further studies are also needed to investigate the material toxicity of nanodrugs to address the issue of clinical translation.

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