Advances in brain-targeted delivery strategies and natural product-mediated enhancement of blood-brain barrier permeability
- J Nanobiotechnology. 2025 May 26;23(1):382. doi: 10.1186/s12951-025-03415-w.
- 1. State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
- 2. NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen, 518057, China.
- 3. NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen, 518057, China. [email protected].
- 4. State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China. [email protected].
- 5. NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation, Shenzhen Institute for Drug Control, Shenzhen, 518057, China. [email protected].
The blood-brain barrier (BBB) represents a formidable challenge in the treatment of neurological disorders, as it restricts the passage of most therapeutic agents into the central nervous system (CNS). Research in brain-targeted delivery strategies and explore in natural products for BBB modulation have opened new avenues for effective CNS Drug Delivery. This review highlights the latest developments in molecular-based delivery systems, cell-based approaches, physical techniques, toxicity concerns, clinical trials and artificial intelligence (AI) -driven modeling for brain-targeted Drug Delivery. Additionally, it examines the role of natural products, particularly aromatic resuscitation medicines, in enhancing BBB permeability through modulating tight junction proteins and inhibiting efflux transporters. It is emphasized that the integration of natural products with modern Drug Delivery systems offers promising opportunities for the development of novel brain-targeted therapies. However, challenges related to the complexity and variety of natural product compositions must be addressed to fully realize their potential. This review underscores the importance of continued research into the molecular mechanisms underlying BBB modulation and natural product-mediated nano-delivery strategies for CNS disorders.