Combined Docetaxel-Loaded Perfluorocarbon Nanodroplets with Ultrasound-Mediated Blood–Brain Barrier Disruption for Effective Glioblastoma Treatment in Mice Model

Introduction: Glioblastoma (GBM) remains the most aggressive primary brain tumor, characterized by a high recurrence rate and a poor prognosis, particularly due to the blood-brain/tumor barrier, which severely limits the intracerebral drug delivery. This study evaluates a novel strategy combining a nanomedicine-based drug delivery approach with focused ultrasound-mediated blood-brain barrier disruption (FUS-BBBD) to achieve localized therapeutic drug concentrations to the tumor. Methods: Paclitaxel and docetaxel were encapsulated in perfluorooctyl bromide nanodroplets, stabilized with fluorinated surfactants. The formulation was optimized and characterized in terms of drug loading, encapsulation efficiency, size, size distribution and stability. In vivo pharmacokinetics (PK) and safety were assessed in C57BL/6 mice. Therapeutic efficacy was evaluated using an orthotopic syngeneic GL261 glioma model combined with hemispheric 1.5 MHz FUS-BBBD. Results: every 72 hours) successfully balanced efficacy and safety, extending median survival to 36 days versus 20 days for free DTX (p < 0.05), while achieving a 33% long-term survival rate. Toxicity was limited to transient and reversible hepatotoxicity. Conclusion: This study demonstrates that the repeated combination of DTX-NDs and FUS-BBBD is a biocompatible and effective strategy for enhancing brain drug delivery while minimizing peripheral toxicity, thereby offering a promising translational approach for the treatment of GBM.