Theranostic Microbubbles with Homogeneous Ligand Distribution for Higher Binding Efficacy

Journal article (2022)

Authors

Bram Meijlink Erasmus MC
Inés Beekers Ortec B.V., Erasmus MC
Mark Olthof Erasmus MC
Ton Van der Steen Erasmus MC
Afw Van der Steen Erasmus MC
AFW van der Steen Erasmus MC
Afw van der Steen Erasmus MC
A van Der Steen Erasmus MC
AFW Van Der Steen Erasmus MC
A Van Der Steen Erasmus MC
AFW van Der Steen Erasmus MC
A Van der Steen Erasmus MC
Afw Van Der Steen Erasmus MC
Ton Van Der Steen Erasmus MC
Afw van Der Steen Erasmus MC
A van der Steen Erasmus MC
Ton van Der Steen Erasmus MC
Ton van der Steen Erasmus MC
AFW Van der Steen Erasmus MC
N De Jong Erasmus MC, ImPhys/Medical Imaging - AS
N. De Jong Erasmus MC, ImPhys/Medical Imaging - AS
N. Jong Erasmus MC, ImPhys/Medical Imaging - AS
N. W. De Jong Erasmus MC, ImPhys/Medical Imaging - AS
N. de Jong Erasmus MC, ImPhys/Medical Imaging - AS
N. de de Jong Erasmus MC, ImPhys/Medical Imaging - AS
Nico Jong Erasmus MC, ImPhys/Medical Imaging - AS
Nico De Jong Erasmus MC, ImPhys/Medical Imaging - AS
N Jong Erasmus MC, ImPhys/Medical Imaging - AS
Nicolaas Jong Erasmus MC, ImPhys/Medical Imaging - AS
N. de De Jong Erasmus MC, ImPhys/Medical Imaging - AS
Nicolaas De Jong Erasmus MC, ImPhys/Medical Imaging - AS
Nico de Jong Erasmus MC, ImPhys/Medical Imaging - AS
N. W. Jong Erasmus MC, ImPhys/Medical Imaging - AS
Nicolaas de Jong Erasmus MC, ImPhys/Medical Imaging - AS
N de Jong Erasmus MC, ImPhys/Medical Imaging - AS
N. W. de Jong Erasmus MC, ImPhys/Medical Imaging - AS
Nico De Jong Erasmus MC, ImPhys/Medical Imaging - AS
Nico De De Jong Erasmus MC, ImPhys/Medical Imaging - AS
Nico De de Jong Erasmus MC, ImPhys/Medical Imaging - AS
N. de Jong Erasmus MC, ImPhys/Medical Imaging - AS
Klazina Kooiman Erasmus MC
Research Group
ImPhys/Medical Imaging (AS) (TU Delft)
Copyright: © 2022 Simone A.G. Langeveld, Bram Meijlink, Inés Beekers, Mark Olthof, A.F.W. van der Steen, N. de Jong, Klazina Kooiman
DOI: https://doi.org/10.3390/pharmaceutics14020311
More Info
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Published Date

2022

Language

English

Faculty

Applied Sciences

Department

ImPhys/Imaging Physics

Research Group

ImPhys/Medical Imaging

Abstract

Phospholipid-coated targeted microbubbles are used for ultrasound molecular imaging and locally enhanced drug delivery, with the binding efficacy being an important trait. The use of organic solvent in microbubble production makes the difference between a heterogeneous or homogeneous ligand distribution. This study demonstrates the effect of ligand distribution on the binding efficacy of phospholipid-coated ανβ3-targeted microbubbles in vitro using a monolayer of human umbilical-vein endothelial cells and in vivo using chicken embryos. Microbubbles with a homogeneous ligand distribution had a higher binding efficacy than those with a heterogeneous ligand distribution both in vitro and in vivo. In vitro, 1.55× more microbubbles with a homogeneous ligand distribution bound under static conditions, while this was 1.49× more under flow with 1.25 dyn/cm2, 1.56× more under flow with 2.22 dyn/cm2, and 1.25× more in vivo. The in vitro dissociation rate of bound microbubbles with homogeneous ligand distribution was lower at low shear stresses (1-5 dyn/cm2). The internalized depth of bound microbubbles was influenced by microbubble size, not by ligand distribution. In conclusion, for optimal binding the use of organic solvent in targeted microbubble production is preferable over directly dispersing phospholipids in aqueous medium.