Intranasal delivery research for CNS diseases shows robust growth, shifting focus to nanoparticles for brain targeting

The blood-brain barrier (BBB) is a formidable biological interface that protects the central nervous system (CNS) but also severely restricts drug delivery to the brain. This limitation hinders effective treatment for numerous CNS disorders, necessitating non-invasive strategies to bypass the BBB. Intranasal administration has emerged as a promising route, offering direct nose-to-brain delivery. However, the rapid expansion of research in this field makes it challenging to identify key trends, emerging technologies, and critical gaps, which this comprehensive review aims to address.

This study performed a comprehensive bibliometric analysis of 4,009 publications on intranasal delivery for CNS diseases, retrieved from the Web of Science Core Collection (WoSCC) between 2000 and 2025. Researchers utilized specialized tools, including VOSviewer, CiteSpace, and R-bibliometrix, to systematically map spatiotemporal trends, analyze collaborative networks among institutions and countries, and track the evolution of keywords. This approach allowed for a holistic understanding of the research landscape and the identification of emerging scientific hotspots.

The analysis revealed a robust upward trend in global research output, with China and the United States predominantly driving this growth. Keyword clustering identified five major research sub-domains: Alzheimer's disease, Oxytocin (focusing on behavioral/psychiatric applications), Stroke and Neuroinflammation, Brain Tumors, and Nanoparticles. Burst detection analysis highlighted a significant paradigm shift in scientific focus over the 25-year period. Early investigations primarily focused on understanding mucosal absorption mechanisms and tolerance. Subsequently, the research transitioned to specific therapeutic agents, such as insulin and oxytocin. Most recently, the field has been dominated by the optimization of delivery vectors.

Specifically, lipid-based nanoparticles and exosomes have become the current technological frontier for enhancing brain targeting, representing a distinct shift in research priorities.