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Multi-physics study of acoustofluidic delivery agents' clustering behavior.

Hussain AlSadiq1, Karnaker Tupally2, Robert Vogel3

  • 1School of Mechanical and Mining Engineering, The University of Queensland, Brisbane, Australia.

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|December 24, 2021
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Summary

Acoustofluidic microbubbles (MBs) and echogenic liposomes (ELIPs) form clusters that diffuse via Brownian motion after ultrasonication stops. This understanding is crucial for optimizing drug delivery systems.

Keywords:
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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Acoustofluidics

Background:

  • Microbubbles (MBs) and echogenic liposomes (ELIPs) are investigated for on-demand drug delivery.
  • Understanding their behavior post-ultrasonication is vital for effective drug release.
  • Acoustofluidics enables precise manipulation of these agents.

Purpose of the Study:

  • Investigate MBs and ELIPs cluster behavior after ultrasonication cessation.
  • Determine the underlying causes of cluster diffusion (electrostatic, steric, Brownian motion).
  • Evaluate existing models for predicting MB attraction velocity for ELIPs.

Main Methods:

  • Tunable resistive pulse sensing (TRPS) for zeta potential and size distribution.
  • Phase analysis light scattering (PALS) for zeta potential measurement.
  • Controlled ultrasonication to induce cluster formation and observe diffusion.

Main Results:

  • Zeta potentials for Definity™ MBs: -2.43 mV (TRPS), -0.62 mV (PALS).
  • Zeta potentials for ELIPs: -3.62 mV (TRPS), -2.35 mV (PALS).
  • Significant cluster formation observed at pressures as low as 6 kPa for both agents.
  • Post-sonication diffusion rates approximated the sum of individual agent diffusion coefficients.
  • De-clustering attributed to Brownian motion, with faster movement for smaller diameters; no electrostatic repulsion observed.

Conclusions:

  • Brownian motion drives de-clustering of MBs and ELIPs post-sonication.
  • Existing models for MB attraction velocity may not directly apply to ELIPs.
  • Findings are critical for designing and optimizing acoustofluidic drug delivery systems.