A novel microbubble delivery platform with high payload of paclitaxel upon focused ultrasound for enhanced glioblastoma treatment

Abstract

Effective chemotherapy for glioblastoma (GBM) is severely limited by the impermeability of the blood-brain barrier (BBB). Although paclitaxel (PTX) demonstrates potent anti-glioma activity in vitro, its poor BBB penetration precludes its clinical use for GBM. We developed a novel PTX-loaded microbubble (PTX@MB) platform designed for targeted drug delivery to gliomas via low-intensity focused ultrasound (LIFU). PTX@MB were fabricated using a perfluorocarbon (PFC) liquid core stabilized by F-127, and their physicochemical properties were characterized. In vitro anti-tumor effects were evaluated using U87MG cells in both 2D culture and 3D spheroid models. For in vivo assessment, an orthotopic U87MG glioma mouse model was utilized. Following intravenous administration of PTX@MB, LIFU was applied to the tumor region to induce localized drug release and transient BBB disruption. Therapeutic outcomes were evaluated by MRI, survival analysis, and histopathology. The fabricated PTX@MB were spherical, with a high drug encapsulation efficiency of 89.1 ± 0.5 %, and exhibited ultrasound-responsive drug release. In vitro, the combination of PTX@MB and ultrasound exposure demonstrated dose-dependent cytotoxicity and significant inhibition of U87MG spheroid growth. In the orthotopic mouse model, the PTX@MB + LIFU treatment significantly suppressed tumor progression and prolonged median survival compared to the control group. The PTX@MB + LIFU system significantly reduced tumor burden without notable systemic toxicity. This ultrasound-responsive platform enables targeted PTX delivery across the BBB and offers a promising, non-invasive strategy for site-specific chemotherapy in neuro-oncology.