DDEL-10. ULTRASOUND-ENHANCED DRUG DELIVERY IN HUMANS ALTERS ENDOTHELIAL PHENOTYPE AND PERTURBS THE ULTRASTRUCTURE OF THE BLOOD BRAIN BARRIER

Abstract The use of low-intensity pulsed ultrasound with concomitant injection microbubbles (LIPU/MB) achieves local and reversible opening the blood-brain barrier (BBB), enhancing delivery systemically administered drugs to brain parenchyma. Electron microscopic studies conducted in animals proposed that LIPU/MB enhances paracellular diffusion across cerebral vasculature, by disrupting tight junction proteins between endothelial cells, as well enhancement caveolar transcytosis. effects on ultrastructure human BBB phenotype have not been systematically investigated. Here we report a first in-human electron study, examining peri-tumoral humans after undergoing LIPU/MB-enhanced drug delivery. Non-eloquent peritumoral was biopsied at different time points (4-63 minutes) following an intraoperative procedure three patients who underwent surgical resection recurrent glioblastoma through phase I clinical trial [NCT04528680]. Transmission microscopy used examine cross sections microvasculature associated components BBB. We observed significant (P = 0.0397) time-dependent decrease frequency caveolae immediately sonication compared non-sonicated control vessels, which resolved within 1 hour treatment. also increase membrane-bound vacuoles cytoplasm 0.0002, one-way ANOVA). Sonicated blood vessels occasionally showed swollen astrocytes, convoluted luminal protections, lightening otherwise dense proteins, frequently biopsies from same patients. Our study shows changes suggests accumulation cells opening.