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

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.

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Publication Details

Journal
Advanced Science
Published
2024-08-29
DOI
https://doi.org/10.1002/advs.202404385
Citations
16
Primary Topic
Ultrasound and Hyperthermia Applications
Type
article
Field-Weighted Citation Impact
2.95

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article

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

Céline Bastard, Susanne Koletnik, Anshuman Dasgupta, Roman A. Barmin et al.
16 citations
Advanced Science
Ultrasound and Hyperthermia Applications
2.95
article

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

Céline Bastard, Susanne Koletnik, Anshuman Dasgupta, Roman A. Barmin, Mirjavad Moosavifar, Thomas Lisson, Alessandro Motta, Georg Schmitz, Fabian M. Kiessling, Roger M. Pallares, Rui Zhang, Anne Rix, Rustam A. Gumerov, Marek Weiler, Jens Koehler, Jasmin Baier, Twan Lammers, Igor I. Potemkin, Elena Rama, M. Pohl, Noah Avraham‐Radermacher, V.G. Kulkarni, Stephan Rütten
article en
16 citations

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.

Advanced ScienceVol. 11(40)
University Hospitals of the Ruhr-University of Bochum (DE), DWI – Leibniz Institute for Interactive Materials (DE), RWTH Aachen University (DE), Ruhr University Bochum (DE)
Australian Government, European Commission, Deutsche Forschungsgemeinschaft, National Science Council, Bundesministerium für Bildung und Forschung, RWTH Aachen University, European Research Council, HORIZON EUROPE European Research Council
Good health and well-being
Openalex Percentile: Top 9%
Ultrasound and Hyperthermia Applications
2.95
DOIOpen Access PDFOpenAlex
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