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

Charlotte L. Nawijn*, Tim Segers, Guillaume Lajoinie, Sigrid Berg, Sofie Snipstad, Catharina de Lange Davies, Michel Versluis

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)1099-1107
Number of pages9
JournalUltrasound in medicine and biology
Volume50
Issue number8
Early online date8 Jun 2024
DOIs
Publication statusPublished - Aug 2024

Keywords

  • UT-Hybrid-D
  • Bright-field microscopy
  • Drug delivery
  • Fluorescence microscopy
  • High-speed imaging
  • Loaded microbubbles
  • Microbubbles
  • Nanomedicine
  • Nanoparticles
  • Ultrasound

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