Enhancing Polymeric Microbubble Monodispersity and Acoustic Responses through Selective Reagent Sourcing.

Abstract

Gas-filled microbubbles (MBs) are widely used as contrast agents for ultrasound (US) imaging and are increasingly being explored for US-mediated drug delivery. Polymeric poly(butyl cyanoacrylate) (PBCA) MBs are particularly well-suited for these applications due to their relatively narrow size distribution, strong acoustic responsiveness, and high drug-loading capacity. While past studies have focused on enhancing the performance of MBs through polymer chemistry, the impact of reagent sourcing has received little attention. The butyl cyanoacrylate monomer, being highly reactive, is commercialized in the presence of chemicals that prevent self-polymerization. As a result, monomers from different suppliers may vary in additives and polymerization characteristics. This study demonstrates that the choice of monomer source strongly affects the size distribution, acoustic response, and payload capability of PBCA MBs. Optimized reagent selection improved the monodispersity of the samples, reducing the half-width at half-maximum of their size distributions from 30 to 16% relative to their diameters. Furthermore, differences in polymer chain length and shell thickness, driven by the monomer source, lead to 180% increases in both drug loading capacity and acoustic responsiveness. These results highlight reagent sourcing as a critical (and previously underappreciated) factor in improving the characteristics and performance of polymeric MBs.