Destruction of Recombinant Tissue Plasminogen Activator (rtPA) -Loaded Echogenic Liposomes under Dual Frequency Sonication

Background:Echogenic liposomes (ELIPs) encapsulate drugs and gas bubbles within lipid vesicles. The destruction of ELIPs in response to MHz and kHz ultrasound waves has been studied previously. Applying ultrasound above a certain threshold causes encapsulated gas bubbles destruct rapidly by fragmentation or more slowly by acoustically driven diffusion. This study compares the destruction of recombinant tissue plasminogen activator (rtPA) -loaded echogenic liposomes using three frequency protocols: 130 kHz, 1 MHz and dual (130 kHz + 1 MHz). Method:In gel phantom, ELIPs were imaged by diagnostic ultrasound system and simultaneously destructive ultrasonic fields were applied at different intensities in each protocol. Images were analyzed. Results:According to the results, 80% decline in MGV (mean of gray value) relative to initial MGV was associated with ELIPs fragmentation. At 130 kHz, results showed an 80% decline in MGV and fragmentation happened at all applied ultrasound intensities (0.01 W/cm2 as fragmentation threshold). In MHz and dual protocols, on average, less than 50% decline in MGV was observed which indicated an acoustically driven diffusion. Conclusion:Our study shows that kHz protocol fragments ELIPs more effectively than other two protocols. For better results, dual frequency protocols need optimized combination of frequencies and phases.