Polymeric Microbubble Shell Engineering: Microporosity as a Key Factor to Enhance Ultrasound Imaging and Drug Delivery Performance

Advanced Science, vol. 11, pp. e2404385

Abstract

Microbubbles (MB) are widely used as contrast agents for ultrasound (US) imaging and US-enhanced drug delivery. Polymeric MB are highly suitable for these applications because of their acoustic responsiveness, high drug loading capability, and ease of surface functionalization. While many studies have focused on using polymeric MB for diagnostic and therapeutic purposes, relatively little attention has thus far been paid to improving their inherent imaging and drug delivery features. This study here shows that manipulating the polymer chemistry of poly(butyl cyanoacrylate) (PBCA) MB via temporarily mixing the monomer with the monomer-mimetic butyl cyanoacetate (BCC) during the polymerization process improves the drug loading capacity of PBCA MB by more than twofold, and the in vitro and in vivo acoustic responses of PBCA MB by more than tenfold. Computer simulations and physisorption experiments show that BCC manipulates the growth of PBCA polymer chains and creates nanocavities in the MB shell, endowing PBCA MB with greater drug entrapment capability and stronger acoustic properties. Notably, because BCC can be readily and completely removed during MB purification, the resulting formulation does not include any residual reagent beyond the ones already present in current PBCA-based MB products, facilitating the potential translation of next-generation PBCA MB.

Authors 21

1. Mirjavad Moosavifar Aachen Institute for Experimental Molecular Imaging

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

   Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

2. Roman A. Barmin Aachen Institute for Experimental Molecular Imaging

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

   Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

3. Elena Rama Aachen Institute for Experimental Molecular Imaging

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

   Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

4. Anne Rix Aachen Institute for Experimental Molecular Imaging

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

   Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

5. Rustam A. Gumerov Aachen DWI - Leibniz Institute for Interactive Materials

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz Institute for Interactive Materials RWTH Aachen University 52074 Aachen Germany

6. Thomas Lisson

   Ruhr University Bochum

   Affiliation as printed

   Chair for Medical Engineering Ruhr University Bochum 44780 Bochum Germany

   Chair for Medical Engineering, Ruhr University Bochum, 44780 Bochum, Germany

7. Céline Bastard Aachen DWI - Leibniz Institute for Interactive Materials

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz Institute for Interactive Materials RWTH Aachen University 52074 Aachen Germany

8. Stephan Rütten Aachen Electron Microscope Facility

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Electron Microscope Facility RWTH Aachen University Hospital 52074 Aachen Germany

   Electron Microscope Facility, RWTH Aachen University Hospital, 52074 Aachen, Germany

9. Noah Avraham‐Radermacher Aachen Institute of Technical and Macromolecular Chemistry

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Institute of Technical and Macromolecular Chemistry RWTH Aachen University Hospital 52074 Aachen Germany

   Institute of Technical and Macromolecular Chemistry, RWTH Aachen University Hospital, 52074 Aachen, Germany

10. Jens Koehler Aachen DWI - Leibniz Institute for Interactive Materials

    DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

    Affiliation as printed

    DWI – Leibniz Institute for Interactive Materials RWTH Aachen University 52074 Aachen Germany

11. Jasmin Baier Aachen Institute for Experimental Molecular Imaging

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

    Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

12. Susanne Koletnik Aachen Institute for Experimental Molecular Imaging

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

    Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

13. Rui Zhang Aachen Institute for Experimental Molecular Imaging

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

    Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

14. Anshuman Dasgupta Aachen Institute for Experimental Molecular Imaging

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

    Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

15. Alessandro Motta Aachen Institute for Experimental Molecular Imaging

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

    Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

16. Marek Weiler Aachen Institute for Experimental Molecular Imaging

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

    Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

17. Igor I. Potemkin Aachen DWI - Leibniz Institute for Interactive Materials

    DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

    Affiliation as printed

    DWI – Leibniz Institute for Interactive Materials RWTH Aachen University 52074 Aachen Germany

18. Georg Schmitz

    Ruhr University Bochum

    Affiliation as printed

    Chair for Medical Engineering Ruhr University Bochum 44780 Bochum Germany

    Chair for Medical Engineering, Ruhr University Bochum, 44780 Bochum, Germany

19. Fabian M. Kiessling Aachen Institute for Experimental Molecular Imaging

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

    Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

20. Twan Lammers corresponding Aachen Institute for Experimental Molecular Imaging

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

    Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

21. Roger M. Pallares corresponding Aachen Institute for Experimental Molecular Imaging

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute for Experimental Molecular Imaging RWTH Aachen University Hospital 52074 Aachen Germany

    Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany

Cited by imported patents 1 (EPO, DOI in their cited literature)

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