Global research trends and hotspots of exosome-mediated drug delivery across the blood-brain barrier: a bibliometric study from 2015 to 2025.

BACKGROUND

The blood-brain barrier (BBB) is a major obstacle to targeted drug delivery for central nervous system (CNS) diseases. Although liposomes and polymeric nanoparticles have improved brain drug delivery, limitations remain in BBB targeting, long-term biocompatibility, and in vivo clearance. Exosomes are endogenous nanoscale extracellular vesicles with favourable biocompatibility, low immunogenicity, and BBB-crossing potential. Therefore, this bibliometric study summarises the current research status, future research trends, and challenges in the more specific field of exosome-mediated BBB drug delivery.

METHODS

A comprehensive search was conducted across the Web of Science Core Collection (WoSCC), PubMed, and Embase databases for relevant English-language literature on exosome-mediated drug delivery across the blood-brain barrier from 2015 to 2025. WoSCC served as the primary source for bibliometric analysis. PubMed and Embase databases were used for supplementary validation. Software such as VOSviewer, CiteSpace, and R-bibliometrix was employed for literature visualisation analysis.

RESULTS

This study included 1,365 relevant articles from the WoSCC database, and the annual publication volume showed a steady upward trend. China and the United States significantly lead in both the number of publications and the number of core contributing institutions in this field. Co-occurrence analysis of keywords showed that research hotspots are mainly focused on exosomes, the blood-brain barrier, drug delivery, and Alzheimer's disease. PubMed and Embase were used as supplementary validation databases, including 1,089 and 1,517 records, respectively. Their annual publication trends, major countries/regions, core journals, and keywords/themes were generally consistent with WoSCC, supporting the macro-level stability of the bibliometric findings.

CONCLUSION

Unlike previous bibliometric analyses that mainly focused on overall trends in CNS exosome research, this study focuses specifically on the direction of exosome-mediated drug delivery across the BBB. The findings show a shift from basic vesicle characterisation toward engineered delivery systems, CNS disease applications, and translational evaluation. Mammalian-derived exosomes remain dominant, while plant-derived vesicles, AI-assisted design, biomimetic hybrid nanovesicles, and gut-brain axis strategies are emerging areas of focus. Future research should prioritise systematic platform comparisons, standardised evaluation, quality control, scalable production, long-term safety, and regulatory pathways.