Long-term physical evolution of an elastomeric ultrasound contrast microbubble

Abstract

Hypothesis One of the main assets of crosslinked polymer-shelled microbubbles (MBs) as ultrasound-active theranostic agents is the robustness of the shells, combined with the chemical versatility in modifying the surface with ligands and/or drugs. Despite the long shelf-life, subtle modifications occur in the MB shells involving shifts in acoustic, mechanical and structural properties. Experiments We carried out a long-term morphological and acoustic evolution analysis on elastomeric polyvinyl-alcohol (PVA)-shelled MBs, a novel platform accomplishing good acoustic and surface performances in one agent. Confocal laser scanning microscopy, acoustic spectroscopy and AFM nanomechanics were integrated to understand the mechanism of PVA MBs ageing. The changes in the MB acoustic properties were framed in terms of shell thickness and viscoelasticity using a linearised oscillation theory, and compared to MB morphology and to nanomechanical analysis. Findings We enlightened a novel, intriguing ageing time evolution of the PVA MBs with double behaviour with respect to a crossover time of ∼50 days. Before, significant changes occur in MB stiffness and shell thickness, mainly due to a massive release of entangled PVA chains. Then, the MB resonance frequency increases together with shell thickening and softening. Our benchmark study is of general interest for emerging viscoelastomeric bubbles towards personalised medicine.

Ultrasound-Stimulated PVA Microbubbles for Adhesive Removal from Cellulose-Based Materials: A Groundbreaking Low-Impact Methodology

“…After each preparation of PVAMBs, the acoustic characterization was also performed as measured by attenuation spectroscopy (not shown) confirming that the acoustic resonance, viscoelastic, and thickness features of the PVAMBs shell are well reproducible compared to the values in the literature. 28 …”

“… 12 , 13 In addition, PVA-shelled microbubbles are very stable and acoustically active, thus representing a versatile tool to enhance the cleaning action with US. 28 , 29 On this basis, we defined a novel strategy for the removal of adhesives from modern paper that combines short-term treatment based on PVA-shelled microbubbles and US treatment, followed by a final cleaning step with hydrogels made up of PVA and telechelic PVA (tel - PVA; see Scheme S1 ). 12 , 13 This is an innovative approach, which makes use of microbubbles coupled with ultrasounds for the selective cleaning of coating from paper.…”

Probing phospholipid microbubbles by atomic force microscopy to quantify bubble mechanics and nanostructural shell properties

“…To truly understand these MBs, which are colloidal systems consisting of lipid-stabilised gas bubbles suspended in an aqueous medium that can resonate at ultrasonic frequencies, it is important to address the physico-chemical properties of the MB shell as this is the key structural element which strongly dictates the quality of the acoustic response. When sonicating with high mechanical index values during ultrasound imaging, the MBs absorb the acoustic energy and begin to oscillatecausing violent expansion and contraction of the bubble (55). Eventually the molecular area of the shell membrane reaches a critical value where it cannot be compressed or expanded any further.…”

Improved hybrid-shelled perfluorocarbon microdroplets as ultrasound- and laser-activated phase-change platform

“…The stabilising shell is directly involved in the bonding with the carried agents (e.g., drugs or functional nanoparticles) and in the targeting towards specific tissues [16,17], it could affect the vaporisation efficiency, and it determines the acoustic response of the MBs formed after vaporisation [18][19][20][21]. On top of these, the primary role of the shell lies in ensuring the stability and the size uniformity of MDs over time.…”