RGD-coated polymeric microbubbles promote ultrasound-mediated drug delivery in an inflamed endothelium-pericyte co-culture model of the blood-brain barrier

• DOI: 10.1007/s13346-024-01561-6
• Publication Date: 2024-03-18T12:02:05Z
• Authors: Christopher Hark; Junlin Chen; Julia Blöck; Eva Miriam Buhl; Harald Radermacher; Robert Pola; Michal Pechar; Tomáš Etrych; Quim Peña; Anne Rix; Natascha I. Drude; Fabian Kiessling; Twan Lammers; Jan-Niklas May
• Keywords: Pericyte; Targeted drug delivery

Abstract Drug delivery to central nervous pathologies is compromised by the blood-brain barrier (BBB). A clinically explored strategy promote drug across BBB sonopermeation, which relies on combined use of ultrasound (US) and microbubbles (MB) induce temporally spatially controlled opening BBB. We developed an advanced in vitro model study impact sonopermeation prototypic polymeric carrier pHPMA as a larger molecule small antiviral ribavirin. This was done under standard inflammatory conditions, employing both untargeted RGD peptide-coated MB. The based human cerebral capillary endothelial cells placental pericytes, are co-cultivated transwell inserts present with proper transendothelial electrical resistance (TEER). Sonopermeation induced significant decrease TEER values facilitated trans-BBB fluorescently labeled (Atto488-pHPMA). To inflamed typical for e.g. tumors, neurodegenerative diseases CNS infections, tumor necrosis factor (TNF) employed inflammation model. RGD-coated MB bound permeabilized endothelium-pericyte co-culture model, potently improved Atto488-pHPMA ribavirin delivery. Taken together, our work combines bioengineering MB-mediated enhancement, thereby providing framework future studies optimization US-mediated brain. Graphical abstract