Ultrasound-Mediated Drug Delivery:Sonoporation Mechanisms,Biophysics,and Critical Factors

Sonoporation,or the use of ultrasound in the presence of cavitation nuclei to induce plasma membrane perforation,is well considered as an emerging physical approach to facilitate the delivery of drugs and genes to living cells.Nevertheless,this emerging drug delivery paradigm has not yet reached widespread clinical use,because the efficiency of sonoporation is often deemed to be mediocre due to the lack of detailed understanding of the pertinent scientific mechanisms.Here,we summarize the current observational evidence available on the notion of sonoporation,and we discuss the prevailing understanding of the physical and biological processes related to sonoporation.To facilitate systematic understanding,we also present how the extent of sonoporation is dependent on a multitude of factors related to acoustic excitation parameters(ultrasound frequency,pressure,cavitation dose,exposure time),microbubble parameters(size,concentration,bubble-to-cell distance,shell composition),and cellular properties(cell type,cell cycle,biochemical contents).By adopting a science-backed approach to the realization of sonoporation,ultrasound-mediated drug delivery can be more controllably achieved to viably enhance drug uptake into living cells with high sonoporation efficiency.This drug delivery approach,when coupled with concurrent advances in ultrasound imaging,has potential to become an effective therapeutic paradigm.

The effect of downstream resistance on flow diverter treatment of a cerebral aneurysm at a bifurcation: A joint computational-experimental study

Intracranial aneurysm can lead to hemorrhagic stroke upon rupture. Deployment of flow diverters can restrict the blood flow into aneurysm and mitigate the rupture risk. Computational fluid dynamics（CFD） and ultrasonography with pulse-wave and color Doppler ultrasound measurements were employed jointly to investigate the complex flow pattern in cerebral aneurysms, both before and after the deployment of flow diverters. Patient-specific configurations of both bifurcation and side-wall aneurysms were selected. The effect of downstream flow resistance was investigated by adjusting the volume flow rate and pressure at the outlet vessels computationally and experimentally. Velocity profiles in the aneurysm measured from ultrasonography showed good agreement with those from computer simulations. The discrepancy in velocity between the computational and experimental sets of data is less than 10%. The downstream resistance can alter the volume flux into a bifurcation aneurysm with a flow diverter deployed by 236%, while the corresponding value of a side-wall aneurysm is negligible. The vorticity of the aneurysmal flow was reduced by more than 80% in both cases after stenting. This study demonstrated that careful investigation of downstream flow resistance of a bifurcation aneurysm is essential to provide an accurate assessment of the aneurysmal flow dynamics after flow diverter deployment.