Oscillatory behavior of microbubbles impacts efficacy of cellular drug delivery

Yi-Ju Ho, Ho Chun Chang, Chia Wei Lin, Ching Hsiang Fan, Yu Chun Lin, Kuo Chen Wei, Chih Kuang Yeh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Drug-loaded microbubbles have been proven to be an effective strategy for non-invasive and local drug delivery when combined with ultrasound excitation for targeted drug release. Inertial cavitation is speculated to be a major mechanism for releasing drugs from drug-loaded microbubbles, but it results in lethal cellular pore damage that greatly limits its application. Thus, we investigated the cellular vesicle attachment and uptake to evaluate the efficiency of drug delivery by modulating the behaviors of targeted microbubble oscillation. The efficiency of vesicle attachment on the targeted cell membrane was 36.5 ± 15.9% and 3.8 ± 2.3% under stable and inertial cavitation, respectively. Further, stable cavitation enhanced cell permeability (26.8 ± 3.2%), maintained cell viability (90.8 ± 2.1%), and showed 7.9 ± 1.9-fold enhancement of in vivo vesicle release on tumor vessels. Therefore, our results reveal the ability to improve drug delivery via stable cavitation induced by targeted microbubbles. We propose that this strategy might be suitable for tissue repair or neuromodulation.

Original languageEnglish
Pages (from-to)316-327
Number of pages12
JournalJournal of Controlled Release
StatePublished - 10 May 2021


  • Drug delivery
  • Inertial cavitation
  • Microbubble
  • Stable cavitation
  • Vesicle release


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