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Neurotherapeutics

, Volume 16, Issue 3, pp 878–890 | Cite as

Characterization and Imaging of Lipid-Shelled Microbubbles for Ultrasound-Triggered Release of Xenon

  • Himanshu ShekharEmail author
  • Arunkumar Palaniappan
  • Tao Peng
  • Maxime Lafond
  • Melanie R. Moody
  • Kevin J. Haworth
  • Shaoling Huang
  • David D. McPherson
  • Christy K. Holland
Original Article
  • 263 Downloads

Abstract

Xenon (Xe) is a bioactive gas capable of reducing and stabilizing neurologic injury in stroke. The goal of this work was to develop lipid-shelled microbubbles for xenon loading and ultrasound-triggered release. Microbubbles loaded with either xenon (Xe-MB) or xenon and octafluoropropane (Xe-OFP-MB) (9:1 v/v) were synthesized by high-shear mixing. The size distribution and the frequency-dependent attenuation coefficient of Xe-MB and Xe-OFP-MB were measured using a Coulter counter and a broadband acoustic attenuation spectroscopy system, respectively. The Xe dose was evaluated using gas chromatography/mass spectrometry. The total Xe doses in Xe-MB and Xe-OFP-MB were 113.1 ± 13.5 and 145.6 ± 25.5 μl per mg of lipid, respectively. Co-encapsulation of OFP increased the total xenon dose, attenuation coefficient, microbubble stability (in an undersaturated solution), and shelf life of the agent. Triggered release of gas payload was demonstrated with 6-MHz duplex Doppler and 220-kHz pulsed ultrasound. These results constitute the first step toward the use of lipid-shelled microbubbles for applications such as neuroprotection in stroke.

Key Words

Bioactive gas delivery xenon delivery lipid-shelled microbubbles ultrasound cytoprotection. 

Notes

Acknowledgments

This work was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke through grant R01 NS047603. Kevin Haworth, Ph.D., was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute through grant K25HL133452. The authors thank Prof. Jack Rubinstein, Dr. Sheryl Koch, and Michelle Nieman for their help with in vivo imaging and Dr. Karla Mercado-Shekhar for assistance with in vitro imaging. Prof. Dong Zhang and Prof. Xiasheng Guo are acknowledged for providing the 220-kHz transducer used in this study, and Robert Kleven for calibrating it. The authors are grateful to Prof. Kenneth Setchell for sharing his expertise on gas chromatography/mass spectroscopy measurements.

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Supplementary material

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2019

Authors and Affiliations

  • Himanshu Shekhar
    • 1
    Email author
  • Arunkumar Palaniappan
    • 1
  • Tao Peng
    • 2
  • Maxime Lafond
    • 1
  • Melanie R. Moody
    • 2
  • Kevin J. Haworth
    • 1
    • 3
  • Shaoling Huang
    • 2
  • David D. McPherson
    • 2
  • Christy K. Holland
    • 1
    • 3
  1. 1.Division of Cardiovascular Health and Disease, Department of Internal MedicineUniversity of CincinnatiCincinnatiUSA
  2. 2.Division of Cardiovascular Medicine, Department of Internal MedicineUniversity of Texas Health Science Center at HoustonHoustonUSA
  3. 3.Department of Biomedical EngineeringUniversity of CincinnatiCincinnatiUSA

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