Focused ultrasound induced blood-brain barrier disruption to enhance chemotherapeutic drugs (BCNU) delivery for glioblastoma treatment

Hao Li Liu*, Mu Yi Hua, Pin Yuan Chen, Chiung Yin Huang, Jiun Jie Wang, Kuo Chen Wei

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

1 Scopus citations

Abstract

Focused ultrasound has been recently found to capable of temporally and reversibly disrupt local blood-brain barrier (BBB) and opens new frontier in delivering varies type of drugs into brain for central nerve system (CNS) disorder treatment. In this study, we aim to investigate the feasibility of delivering 1, 3-bits (2-chloroethyl) -1-nitrosourea (BCNU) to treat glioblastoma in animal models and evaluate whether this approach would gain treatment efficacy. Under the presence of microbubbles administration, a 400-kHz focused ultrasound was employed to deliver burst-tone ultrasonic energy stimulation to disrupt BBB in animal brains transcranially, and in-vivo monitored by magnetic-resonance imaging (MRI). C6-glioma cells were cultured and implanted into Sprague-Dawley rats as the brain-tumor model. BCNU deposited in brain was quantified by using high-performance liquid chromatography (HPLC), and brain tissues were examined histologically. MRI was employed to longitudinal evaluate the brain tumor treatment including the analysis of tumor progression and animal survival. We confirmed that the focused ultrasound, under the secure ultrasonic energy level, can significantly enhance the BCNU penetration through BBB over 300% than control without cause hemorrhage. Apparent improvement of treatment efficacy achieved by combining focused ultrasound with BCNU delivery, including significant suppression of tumor growth and a prolonged animal survival. This study highly support that this treatment strategy could be clinically-relevant and may help to provide another potential strategy in increasing local chemotherapeutic drugs for brain-tumor treatment.

Original languageEnglish
Title of host publication9th International Symposium on Therapeutic Ultrasound - ISTU 2009
Pages176-181
Number of pages6
DOIs
StatePublished - 2010
Event9th International Symposium on Therapeutic Ultrasound, ISTU 2009 - Aix-en-Provence, France
Duration: 24 09 200926 09 2009

Publication series

NameAIP Conference Proceedings
Volume1215
ISSN (Print)0094-243X
ISSN (Electronic)1551-7616

Conference

Conference9th International Symposium on Therapeutic Ultrasound, ISTU 2009
Country/TerritoryFrance
CityAix-en-Provence
Period24/09/0926/09/09

Keywords

  • BCNU
  • Blood-brain barrier
  • Brain tumor
  • Drug delivery
  • Focused ultrasound

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