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High-Speed Optical Characterization of Protein-and-Nanoparticle–Stabilized Microbubbles for Ultrasound-Triggered Drug Release

Abstract

Objective: Ultrasound-triggered bubble-mediated local drug delivery has shown potential to increase therapeutic efficacy and reduce systemic side effects, by loading drugs into the microbubble shell and triggering delivery of the payload on demand using ultrasound. Understanding the behavior of the microbubbles in response to ultrasound is crucial for efficient and controlled release. Methods: In this work, the response of microbubbles with a coating consisting of poly(2-ethyl-butyl cyanoacrylate) (PEBCA) nanoparticles and denatured casein was characterized. High-speed recordings were taken of single microbubbles, in both bright field and fluorescence. Results: The nanoparticle-loaded microbubbles show resonance behavior, but with a large variation in response, revealing a substantial interbubble variation in mechanical shell properties. The probability of shell rupture and the probability of nanoparticle release were found to strongly depend on microbubble size, and the most effective size was inversely proportional to the driving frequency. The probabilities of both rupture and release increased with increasing driving pressure amplitude. Rupture of the microbubble shell occurred after fewer cycles of ultrasound as the driving pressure amplitude or driving frequency was increased. Conclusion: The results highlight the importance of careful selection of the driving frequency, driving pressure amplitude and duration of ultrasound to achieve the most efficient ultrasound-triggered shell rupture and nanoparticle release of protein-and-nanoparticle–stabilized microbubbles.
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Category

Academic article

Language

English

Author(s)

  • Charlotte Nawijn
  • Tim Segers
  • Guillaume Lajoinie
  • Sigrid Berg
  • Sofie Snipstad
  • Catharina de Lange Davies
  • Michel Versluis

Affiliation

  • SINTEF Industry / Biotechnology and Nanomedicine
  • SINTEF Digital / Health Research
  • University of Twente, Enschede
  • St. Olavs Hospital, Trondheim University Hospital
  • Norwegian University of Science and Technology

Year

2024

Published in

Ultrasound in Medicine and Biology

ISSN

0301-5629

Volume

50

Issue

8

Page(s)

1099 - 1107

View this publication at Norwegian Research Information Repository