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Related Experiment Video

Updated: Jun 30, 2025

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Determining Ultrasound Parameters for Bursting Polymer Microbubbles for Future Use in Spinal Cord Injury.

Brian E Oeffinger1, Maria Stanczak2, Angelo C Lepore3

  • 1School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, USA.

Ultrasound in Medicine & Biology
|March 22, 2024
PubMed
Summary

Poly(lactic acid) microbubbles offer a promising method for targeted drug delivery in spinal cord injury (SCI) treatment. Ultrasound-triggered bursting of these microbubbles enables safe and effective in situ therapeutic delivery.

Keywords:
BurstingDrug deliveryMicrobubbleSpinal cord injuryUltrasound

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Area of Science:

  • Biomaterials Science
  • Ultrasound Technology
  • Drug Delivery Systems

Background:

  • Spinal cord injury (SCI) presents significant challenges for effective therapeutic delivery.
  • Current methods for intrathecal drug delivery to the spinal cord are often limited in targeting and efficiency.
  • Microbubbles have emerged as potential carriers for targeted therapeutic applications.

Purpose of the Study:

  • To investigate the feasibility of using poly(lactic acid) (PLA) microbubbles for ultrasound-triggered therapeutic delivery to SCI.
  • To determine optimal in vitro ultrasound bursting parameters for PLA microbubbles.
  • To assess the loading and release of a model bioactive DNA (oligonucleotide) from PLA microbubbles.

Main Methods:

  • PLA microbubbles were fabricated using ammonium carbonate and ammonium carbamate as porogens.
  • Ultrasound exposure in a rat cadaver SCI model was used to assess in situ bursting.
  • Burst pressure thresholds, resonance frequency, acoustic enhancement, sizing, and morphology were evaluated.
  • Oligonucleotides were loaded into the microbubble shells and released using optimized ultrasound parameters.

Main Results:

  • In situ imaging and bursting of PLA microbubbles were successful.
  • Optimal in vitro bursting occurred near the resonance frequency (2.5-3.0 MHz) using 2.25 MHz ultrasound at safe peak negative pressures (0.2-0.5 MPa).
  • Ultrasound bursting resulted in significant oligonucleotide release, with microbubbles collapsing to 0.5-1 µm without fragmentation. Ammonium carbonate yielded more accurate measurements than ammonium carbamate.

Conclusions:

  • Poly(lactic acid) microbubbles, when produced with ammonium carbonate and burst using optimized ultrasound parameters, demonstrate potential for safe and improved intrathecal therapeutic delivery for SCI.
  • Targeted ultrasound-triggered bursting offers a promising approach for localized drug delivery to the spinal cord.
  • Further research is warranted to translate this technology into clinical practice for SCI treatment.