Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse

Fluids and Barriers of the CNS

Chueh-Hung Wu¹  Yi Kung¹  Ming-Yen Hsiao¹  Wei-Hao Liao¹  Wen-Shiang Chen²  Abel P.-H. Huang³  Yi-Hua Hsu³  Kuan-Yu Chen⁴ 

[1] Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of Medicine, Taipei City, Taiwan;Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital & National Taiwan University College of Medicine, Taipei City, Taiwan;Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan;Department of Surgery, National Taiwan University Hospital, Taipei City, Taiwan;Division of Pulmonology, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan;

关键词: Low-energy extracorporeal focused shockwave pulse;    Blood–brain barrier;    Blood-cerebrospinal fluid barrier;    Central nervous system;    Glioblastoma multiforme;    Leptomeningeal carcinomatosis;   

DOI  :  10.1186/s12987-021-00303-x

来源: Springer

【 摘 要 】

BackgroundThe blood-cerebrospinal fluid (CSF) barrier (BCSFB) is critically important to the pathophysiology of the central nervous system (CNS). However, this barrier prevents the safe transmission of beneficial drugs from the blood to the CSF and thus the spinal cord and brain, limiting their effectiveness in treating a variety of CNS diseases.MethodsThis study demonstrates a method on SD rats for reversible and site-specific opening of the BCSFB via a noninvasive, low-energy focused shockwave (FSW) pulse (energy flux density 0.03 mJ/mm2) with SonoVue microbubbles (2 × 106 MBs/kg), posing a low risk of injury.ResultsBy opening the BCSFB, the concentrations of certain CNS-impermeable indicators (70 kDa Evans blue and 500 kDa FITC-dextran) and drugs (penicillin G, doxorubicin, and bevacizumab) could be significantly elevated in the CSF around both the brain and the spinal cord. Moreover, glioblastoma model rats treated by doxorubicin with this FSW-induced BCSFB (FSW-BCSFB) opening technique also survived significantly longer than untreated controls.ConclusionThis is the first study to demonstrate and validate a method for noninvasively and selectively opening the BCSFB to enhance drug delivery into CSF circulation. Potential applications may include treatments for neurodegenerative diseases, CNS infections, brain tumors, and leptomeningeal carcinomatosis.

【 授权许可】

CC BY