期刊
BIOMATERIALS
卷 206, 期 -, 页码 73-86出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.03.021
关键词
Focused ultrasound; Clinically translatable; Targeted drug delivery; Noninvasive ultrasonic drug uncaging; Drug delivery platform; Spatiotemporally controlled release
资金
- National Institutes of Health (BRAIN Initiative) [RF1 MH114252]
- National Cancer Institute/Stanford Center for Cancer Nanotechnology Excellence [NIH U54 CA199075]
- Dana Foundation
- Foundation of the American Society for Neuroradiology
- Wallace H. Coulter Foundation
- Stanford Neurosciences Institute
Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness and relatively broad drug spatial distribution. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body with high spatial and temporal precision. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle meet these needs, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs, beyond a few niche applications. Here, we develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted delivery of hydrophobic drugs with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that are scalable and yield sterile, stable, and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, we exhibit a new potential application of these nanoemulsions for local control of vascular tone. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for efficacious, noninvasive, and localized ultrasonic drug uncaging for myriad targets in the brain and body.
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