Focused ultrasound induced blood‐brain barrier disruption to enhance chemotherapeutic drugs (BCNU) delivery for glioblastoma treatment
- Conference date: 24–26 September 2009
- Location: Aix‐en‐Provence (France)
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.
- Drug delivery
- Magnetic resonance imaging
- Central nervous system
- Comparative animal models
- Fluid bubbles
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