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Communication Dans Un Congrès Année : 2020

Ultrasound-driven microbubbles for local drug delivery

Résumé

In ultrasound-mediated drug delivery, bubbles decorated with a functional payload are convenient transport vehicles and offer highly localized release. These bubbles are traceable using ultrasound, can be activated on demand and protect their cargo from the natural clearing mechanisms of the body. In addition, microbubbles offer an active way to mechanically overcome biological barriers. Such microbubbles are therefore being extensively investigated for single cell, gene and cancer therapy. Experimental investigation of microbubble interactions with cell monolayers has led to the description of a phenomenon termed ?sonoprinting?: confocal imaging shows how exposure of the microbubbles to ultrasound can result in the deposition of their payload in patches onto the cell membrane. In parallel, investigation of single microbubbles with a combination of ultra-high-speed imaging at 10 million frames per second, and high-speed fluorescence imaging at 50,000 frames per second demonstrates how non-spherical bubble oscillations induce both, the release of the drug payload and its transport by microbubble-induced streaming. These observations are validated with a simple theoretical model based on the Rayleigh-Plesset equation. In order to reconcile these observations, we combine three optical imaging techniques to capture the bubble-cell interactions on timescales ranging from sub-microseconds to several seconds. We observe that non-spherically oscillating microbubbles release their nanoparticle payload in the first few ultrasound cycles. At low pressures, the released nanoparticles are transported away by microstreaming, as observed for single microbubbles. This configuration, however, does not favor of the nanoparticles uptake. Higher pressures (> 300 kPa) and longer ultrasound pulses (>100 cycles) lead to rapid translation of the microbubbles and transport of the released nanoparticles in the microbubbles wake, eventually leading to the deposition of nanoparticles in elongated patches onto the cell membrane.
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Dates et versions

hal-03240367 , version 1 (29-05-2021)

Identifiants

Citer

Guillaume Lajoinie, Silke Roovers, Ine De Cock, Ying Luan, Erik Gelderblom, et al.. Ultrasound-driven microbubbles for local drug delivery. Forum Acusticum, Dec 2020, Lyon, France. pp.1091-1095, ⟨10.48465/fa.2020.1108⟩. ⟨hal-03240367⟩
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