Microbubbles for human diagnosis and therapy

Fournier, Louise; Taille, Thibault de La; Chauvierre, Cédric

doi:10.1016/j.biomaterials.2023.122025

Cited by 31 publications

(11 citation statements)

References 254 publications

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“…The former is a device specifically designed for the activation of Definity ® samples through mechanical agitation, under a controlled shaking rate and duration, of a solution of the shell material in a sealed vial with the headspace filled with the core gas. The latter is an immersion homogenizer that exploits the shear force of its tip to form MBs via rotor/stator homogenization [42]. To be precise, the Polytron dispersion procedure previously reported by Gazzera et al [38] was slightly modified and adapted to the smaller volumes of HFBII solutions used in the current work.…”

Section: Comparison Between the Vialmix™ And Polytron Preparation Met...mentioning

confidence: 99%

Hydrophobin-Coated Perfluorocarbon Microbubbles with Strong Non-Linear Acoustic Response

Dichiarante,

Salzano,

Bussat

et al. 2024

Chemistry

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Gas-filled microbubbles are well-established contrast agents for ultrasound imaging and widely studied as delivery systems for theranostics. Herein, we have demonstrated the promising potential of the hydrophobin HFBII—a fungal amphiphilic protein—in stabilizing microbubbles with various fluorinated core gases. A thorough screening of several experimental parameters was performed to find the optimized conditions regarding the preparation technique, type of core gas, HFBII initial concentration, and protein dissolution procedure. The best results were obtained by combining perfluorobutane (C4F10) gas with 1 mg/mL of aqueous HFBII, which afforded a total bubble concentration higher than 109 bubbles/mL, with long-term stability in solution (at least 3 h). Acoustic characterization of such microbubbles in the typical ultrasound frequency range used for diagnostic imaging showed the lower pressure resistance of HFBII microbubbles, if compared to conventional ones stabilized by phospholipid shells, but, at the same time, revealed strong non-linear behavior, with a significant harmonic response already at low acoustic pressures. These findings suggest the possibility of further improving the performance of HFBII-coated perfluorinated gas microbubbles, for instance by mixing the protein with other stabilizing agents, e.g., phospholipids, in order to tune the viscoelastic properties of the outer shell.

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Section: Comparison Between the Vialmix™ And Polytron Preparation Met...mentioning

confidence: 99%

Hydrophobin-Coated Perfluorocarbon Microbubbles with Strong Non-Linear Acoustic Response

Dichiarante,

Salzano,

Bussat

et al. 2024

Chemistry

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“…The in vivo imaging experiments were conducted using a PHILIPS EPIQ 7 ultrasound diagnostic system (PHILIPS, Tokyo, Japan) equipped with a L12-5 linear array transducer (5)(6)(7)(8)(9)(10)(11)(12). In response to the results of ultrasound imaging in vitro, a MI of 0.08 was selected for the contrast-enhanced imaging of MBs in SD rat livers and kidneys.…”

Section: In Vivo Ultrasound Imagingmentioning

confidence: 99%

“…At a low mechanical index, steady-state cavitation mostly occurs in MBs, resulting in lasting enhancement. When a higher mechanical index is applied, the ultrasonic energy is sufficient to rupture smaller-sized MBs, leading to shorter acoustic enhancement [11]. Thus, there is still an urgent need for ideal UCAs that provide higher echo intensity and mechanical index (MI) tolerance.…”

Section: Introductionmentioning

confidence: 99%

The Green Synthesis of Reduced Graphene Oxide Using Ellagic Acid: Improving the Contrast-Enhancing Effect of Microbubbles in Ultrasound

Cheng,

Wang,

Zhou

et al. 2023

Molecules

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There is an urgent need to realize precise clinical ultrasound with ultrasound contrast agents that provide high echo intensity and mechanical index tolerance. Graphene derivatives possess exceptional characteristics, exhibiting great potential in fabricating ideal ultrasound contrast agents. Herein, we reported a facile and green approach to synthesizing reduced graphene oxide with ellagic acid (rGO-EA). To investigate the application of a graphene derivative in ultrasound contrast agents, rGO-EA was dispersed in saline solution and mixed with SonoVue (SV) to fabricate SV@rGO-EA microbubbles. To determine the properties of the product, analyses were performed, including ultraviolet–visible spectroscopy (UV–vis), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), X-ray photoelectron spectrum (XPS), X-ray diffraction analysis (XRD) and zeta potential analysis. Additionally, cell viability measurements and a hemolysis assay were conducted for a biosafety evaluation. SV@rGO-EA microbubbles were scanned at various mechanical index values to obtain the B-mode and contrast-enhanced ultrasound (CEUS) mode images in vitro. SV@rGO-EA microbubbles were administered to SD rats, and their livers and kidneys were imaged in CEUS and B-mode. The absorption of rGO-EA resulted in an enhanced echo intensity and mechanical index tolerance of SV@rGO-EA, surpassing the performance of SV microbubbles both in vitro and in vivo. This work exhibited the application potential of graphene derivatives in the field of ultrasound precision medicine.

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“…Microbubbles (MBs) are 1–10 μm diameter gas-filled microspheres, typically comprising a perfluorocarbon gas core and a thin stabilizing shell of phospholipid, protein, or polymer. − Owing to their versatile acoustic behavior, MBs hold great promise for ultrasound imaging and therapy. − However, whether utilized in clinical or research practice, challenges persist in their formulations, characterized by limited in vivo circulation (usually 2–5 min) and variations in composition, size distribution, concentration, and recommended dosage. , These variations result in diverse acoustic responses, , biological effects, , and biomedical outcomes, − prompting the need to reveal interrelationships between MB composition and biointeractions while minimizing confounding effects of MB size distribution and dose. Such discoveries may inspire innovative approaches to extend MB circulation persistence, improve pharmacokinetics, establish standardized dosing, and enhance clinical utility.…”

Section: Introductionmentioning

confidence: 99%

Effect of Poly(ethylene glycol) Configuration on Microbubble Pharmacokinetics

Navarro-Becerra,

Castillo,

Borden

2024

ACS Biomater. Sci. Eng.

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Microbubbles (MBs) hold substantial promise for medical imaging and therapy; nonetheless, knowledge gaps persist between composition, structure, and in vivo performance, especially with respect to pharmacokinetics. Of particular interest is the role of the poly(ethylene glycol) (PEG) layer, which is thought to shield the MB against opsonization and rapid clearance but is also known to cause an antibody response upon multiple injections. The goal of this study was, therefore, to elucidate the role of the PEG layer in circulation persistence of MBs in the nai ̈ve animal (prior to an adaptive immune response). Here, we directly observe the number and size of individual MBs obtained from blood samples, unifying size and concentration into the microbubble volume dose (MVD) parameter. This approach enables direct evaluation of the pharmacokinetics of intact MBs, comprising both the lipid shell and gaseous core, rather than separately assessing the lipid or gas components. We examined the in vivo circulation persistence of 3 μm diameter phospholipid-coated MBs with three different mPEG 2000 content: 2 mol % (mushroom), 5 mol % (intermediate), and 10 mol % (brush). MB size and concentration in the blood were evaluated by a hemocytometer analysis over 30 min following intravenous injections of 20 and 40 μL/kg MVD in Sprague−Dawley rats. Interestingly, pharmacokinetic analysis demonstrated that increasing PEG concentration on the MB surface resulted in faster clearance. This was evidenced by a 1.6-fold reduction in half-life and area under the curve (AUC) (p < 0.05) in the central compartment. Conversely, the AUC in the peripheral compartment increased with PEG density, suggesting enhanced MB trapping by the mononuclear phagocyte system. This was supported by an in vitro assay, which showed a significant rise in complement C3a activation with a higher PEG content. In conclusion, a minimal PEG concentration on the MB shell (mushroom configuration) was found to prolong circulation and mitigate immunogenicity.

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Microbubbles for human diagnosis and therapy

Cited by 31 publications

References 254 publications

Hydrophobin-Coated Perfluorocarbon Microbubbles with Strong Non-Linear Acoustic Response

Hydrophobin-Coated Perfluorocarbon Microbubbles with Strong Non-Linear Acoustic Response

The Green Synthesis of Reduced Graphene Oxide Using Ellagic Acid: Improving the Contrast-Enhancing Effect of Microbubbles in Ultrasound

Effect of Poly(ethylene glycol) Configuration on Microbubble Pharmacokinetics

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