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

被引：3

作者：

Moosavifar, Mirjavad ^{[1
]}

Barmin, Roman A. ^{[1
]}

Rama, Elena ^{[1
]}

Rix, Anne ^{[1
]}

Gumerov, Rustam A. ^{[2
]}

Lisson, Thomas ^{[3
]}

Bastard, Celine ^{[2
]}

Ruetten, Stephan ^{[4
]}

Avraham-Radermacher, Noah ^{[5
]}

Koehler, Jens ^{[2
]}

Pohl, Michael ^{[2
]}

Kulkarni, Vedangi ^{[1
]}

Baier, Jasmin ^{[1
]}

Koletnik, Susanne ^{[1
]}

Zhang, Rui ^{[1
]}

Dasgupta, Anshuman ^{[1
]}

Motta, Alessandro ^{[1
]}

Weiler, Marek ^{[1
]}

Potemkin, Igor I. ^{[2
]}

Schmitz, Georg ^{[3
]}

Kiessling, Fabian ^{[1
]}

Lammers, Twan ^{[1
]}

Pallares, Roger M. ^{[1
]}

机构：

[1] RWTH Aachen Univ Hosp, Inst Expt Mol Imaging, D-52074 Aachen, Germany

[2] Rhein Westfal TH Aachen, Leibniz Inst Interact Mat, DWI, D-52074 Aachen, Germany

[3] Ruhr Univ Bochum, Chair Med Engn, D-44780 Bochum, Germany

[4] RWTH Aachen Univ Hosp, Electron Microscope Facil, D-52074 Aachen, Germany

[5] RWTH Aachen Univ Hosp, Inst Tech & Macromol Chem, D-52074 Aachen, Germany

来源：

ADVANCED SCIENCE | 2024年 / 11卷 / 40期

基金：

欧洲研究理事会;

关键词：

drug delivery; drug loading; microbubbles; PBCA; ultrasound; CONTRAST AGENTS; TRIGGERED DRUG; LOADED MICROBUBBLES; DOXORUBICIN; COUMARIN; SONOPORATION; MECHANISMS; THERAPY;

D O I：

10.1002/advs.202404385

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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. Microbubbles (MB) are widely used in the clinic as contrast agents for ultrasound imaging (US), and they are increasingly explored for US-enhanced drug delivery. This study here demonstrated that washable monomer-mimetic chemicals can be used to manipulate the polymer chemistry of poly(butyl cyanoacrylate) MB, maximizing their performance in US imaging and drug delivery. image

引用

页数：13

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