Ultrasound actuated neuropeptide delivery across cerebrovascular interfaces using phase-change peptide nanoemulsions.

Targeted delivery of neuromodulatory biomacromolecules, such as neuropeptides, to selective brain regions holds promise to treat various neuropathologies and neuropsychiatric disorders. Accordingly, novel transport strategies that can shuttle biotherapeutics across the tightly regulated neurovascular barrier remains an urgent need. Here, we report phase-changing peptide nanoemulsions that ballistically deliver encapsulated neuropeptides across endothelial interfaces under ultrasound (US)-induced vaporization. Utilizing the neuropeptide somatostatin as an exemplary cargo, in vitro and ex vivo studies demonstrate this strategy enables safe and effective trans-endothelial transport of encapsulated biologics with spatiotemporal control. These findings suggest that, with continued development, this platform may advance non-invasive, safe, and spatially precise delivery modalities for challenging macromolecular therapeutics to central nervous tissues.