» Articles » PMID: 38464996

Drug Delivery to the Central Nervous System

Overview
Journal Nat Rev Mater
Date 2024 Mar 11
PMID 38464996
Authors
Affiliations
Soon will be listed here.
Abstract

Despite the rising global incidence of central nervous system (CNS) disorders, CNS drug development remains challenging, with high costs, long pathways to clinical use and high failure rates. The CNS is highly protected by physiological barriers, in particular, the blood-brain barrier and the blood-cerebrospinal fluid barrier, which limit access of most drugs. Biomaterials can be designed to bypass or traverse these barriers, enabling the controlled delivery of drugs into the CNS. In this Review, we first examine the effects of normal and diseased CNS physiology on drug delivery to the brain and spinal cord. We then discuss CNS drug delivery designs and materials that are administered systemically, directly to the CNS, intranasally or peripherally through intramuscular injections. Finally, we highlight important challenges and opportunities for materials design for drug delivery to the CNS and the anticipated clinical impact of CNS drug delivery.

Citing Articles

The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer's disease.

Quan S, Fu X, Cai H, Ren Z, Xu Y, Jia L Mol Neurodegener. 2025; 20(1):25.

PMID: 40038765 PMC: 11877805. DOI: 10.1186/s13024-025-00815-2.


Biology, Pathology, and Targeted Therapy of Exosomal Cargoes in Parkinson's Disease: Advances and Challenges.

Almasi F, Abbasloo F, Soltani N, Dehbozorgi M, Moghadam Fard A, Kiani A Mol Neurobiol. 2025; .

PMID: 39998798 DOI: 10.1007/s12035-025-04788-7.


Metal nanoparticles in neuroinflammation: impact on microglial dynamics and CNS function.

Alaei M, Koushki K, Taebi K, Yousefi Taba M, Keshavarz Hedayati S, Shahbaz S RSC Adv. 2025; 15(7):5426-5451.

PMID: 39967886 PMC: 11833603. DOI: 10.1039/d4ra07798a.


Blood-brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system.

Wang C, Xue Y, Markovic T, Li H, Wang S, Zhong Y Nat Mater. 2025; .

PMID: 39962245 DOI: 10.1038/s41563-024-02114-5.


Pooled screening for CAR function identifies novel IL-13Rα2-targeted CARs for treatment of glioblastoma.

Gordon K, Perez C, Garmilla A, Lam M, Aw J, Datta A J Immunother Cancer. 2025; 13(2).

PMID: 39933837 PMC: 11815465. DOI: 10.1136/jitc-2024-009574.


References
1.
Carpentier A, Canney M, Vignot A, Reina V, Beccaria K, Horodyckid C . Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci Transl Med. 2016; 8(343):343re2. DOI: 10.1126/scitranslmed.aaf6086. View

2.
Chu C, Jablonska A, Lesniak W, Thomas A, Lan X, Linville R . Optimization of osmotic blood-brain barrier opening to enable intravital microscopy studies on drug delivery in mouse cortex. J Control Release. 2019; 317:312-321. DOI: 10.1016/j.jconrel.2019.11.019. View

3.
Marcos-Contreras O, Brenner J, Kiseleva R, Zuluaga-Ramirez V, Greineder C, Villa C . Combining vascular targeting and the local first pass provides 100-fold higher uptake of ICAM-1-targeted vs untargeted nanocarriers in the inflamed brain. J Control Release. 2019; 301:54-61. PMC: 6510023. DOI: 10.1016/j.jconrel.2019.03.008. View

4.
Stewart G, Taylor M, Johnson R, Chellman G . Hyperplastic changes within the leptomeninges of the rat and monkey in response to chronic intracerebroventricular infusion of nerve growth factor. Exp Neurol. 1997; 145(1):24-37. DOI: 10.1006/exnr.1997.6448. View

5.
Vanlandewijck M, He L, Mae M, Andrae J, Ando K, Del Gaudio F . A molecular atlas of cell types and zonation in the brain vasculature. Nature. 2018; 554(7693):475-480. DOI: 10.1038/nature25739. View