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Article

The Impact of Lipid Handling and Phase Distribution on the Acoustic Behavior of Microbubbles

1
Thorax Center, Biomedical Engineering, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands
2
Acoustical Wavefield Imaging, Delft University of Technology, 2628 CJ Delft, The Netherlands
*
Author to whom correspondence should be addressed.
Pharmaceutics 2021, 13(1), 119; https://doi.org/10.3390/pharmaceutics13010119
Received: 18 December 2020 / Revised: 13 January 2021 / Accepted: 14 January 2021 / Published: 19 January 2021
(This article belongs to the Special Issue Preclinical Evaluation of Lipid-Based Nanosystems)
Phospholipid-coated microbubbles are ultrasound contrast agents that can be employed for ultrasound molecular imaging and drug delivery. For safe and effective implementation, microbubbles must respond uniformly and predictably to ultrasound. Therefore, we investigated how lipid handling and phase distribution affected the variability in the acoustic behavior of microbubbles. Cholesterol was used to modify the lateral molecular packing of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)-based microbubbles. To assess the effect of lipid handling, microbubbles were produced by a direct method, i.e., lipids directly dispersed in an aqueous medium or indirect method, i.e., lipids first dissolved in an organic solvent. The lipid phase and ligand distribution in the microbubble coating were investigated using confocal microscopy, and the acoustic response was recorded with the Brandaris 128 ultra-high-speed camera. In microbubbles with 12 mol% cholesterol, the lipids were miscible and all in the same phase, which resulted in more buckle formation, lower shell elasticity and higher shell viscosity. Indirect DSPC microbubbles had a more uniform response to ultrasound than direct DSPC and indirect DSPC-cholesterol microbubbles. The difference in lipid handling between direct and indirect DSPC microbubbles significantly affected the acoustic behavior. Indirect DSPC microbubbles are the most promising candidate for ultrasound molecular imaging and drug delivery applications. View Full-Text
Keywords: ultrasound contrast agents; phospholipid coating; ligand distribution; cholesterol; acoustic response; microbubble; lipid phase ultrasound contrast agents; phospholipid coating; ligand distribution; cholesterol; acoustic response; microbubble; lipid phase
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MDPI and ACS Style

Langeveld, S.A.G.; Beekers, I.; Collado-Lara, G.; van der Steen, A.F.W.; de Jong, N.; Kooiman, K. The Impact of Lipid Handling and Phase Distribution on the Acoustic Behavior of Microbubbles. Pharmaceutics 2021, 13, 119. https://doi.org/10.3390/pharmaceutics13010119

AMA Style

Langeveld SAG, Beekers I, Collado-Lara G, van der Steen AFW, de Jong N, Kooiman K. The Impact of Lipid Handling and Phase Distribution on the Acoustic Behavior of Microbubbles. Pharmaceutics. 2021; 13(1):119. https://doi.org/10.3390/pharmaceutics13010119

Chicago/Turabian Style

Langeveld, Simone A.G., Inés Beekers, Gonzalo Collado-Lara, Antonius F.W. van der Steen, Nico de Jong, and Klazina Kooiman. 2021. "The Impact of Lipid Handling and Phase Distribution on the Acoustic Behavior of Microbubbles" Pharmaceutics 13, no. 1: 119. https://doi.org/10.3390/pharmaceutics13010119

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