Biomaterials, Controlled Release, Drug Delivery, Ultrasound Response
This work was supported by a grant from the National Institutes of Health (NIH) (2 R01 DE013349). S.K.’s contributions were partially supported by start-up funds from the College of Engineering at the University of Rhode Island, an Early Career Development Award from the Rhode Island IDeA Network for Biomedical Research Excellence (RI-INBRE, NIH National Institute of General Medical Sciences, 2 P20 GM103430), a Medical Research Grant from the Rhode Island Foundation (20144262), and an EPSCoR Track II grant from the National Science Foundation (1539068). C.K. acknowledges a Royal College of Surgeons’ Office of Research and Innovation Seed Fund Award (GR 14-0963), a Science Foundation Ireland (SFI) grant (SFI/12/RC/2278), and the European Union for a Marie Curie European Reintegration Grant under H2020 (Project Reference 659715). H.S. acknowledges the Fulbright Program.
In many biomedical contexts ranging from chemotherapy to tissue engineering, it is beneficial to sequentially present bioactive payloads. Explicit control over the timing and dose of these presentations is highly desirable. Here, we present a capsule-based delivery system capable of rapidly releasing multiple payloads in response to ultrasonic signals. In vitro, these alginate capsules exhibited excellent payload retention for up to 1 week when unstimulated and delivered their entire payloads when ultrasonically stimulated for 10-100 s. Shorter exposures (10 s) were required to trigger delivery from capsules embedded in hydrogels placed in a tissue model and did not result in tissue heating or death of encapsulated cells. Different types of capsules were tuned to rupture in response to different ultrasonic stimuli, thus permitting the sequential, on-demand delivery of nanoparticle payloads. As a proof of concept, gold nanoparticles were decorated with bone morphogenetic protein-2 to demonstrate the potential bioactivity of nanoparticle payloads. These nanoparticles were not cytotoxic and induced an osteogenic response in mouse mesenchymal stem cells. This system may enable researchers and physicians to remotely regulate the timing, dose, and sequence of drug delivery on-demand, with a wide range of clinical applications ranging from tissue engineering to cancer treatment.
Kennedy S, Hu J, Kearney C, Skaat H, Gu L, Gentili M, Vandenburgh H, Mooney D. Sequential release of nanoparticle payloads from ultrasonically burstable capsules. Biomaterials. 2016;75:91-101.
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