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

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). 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. 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. 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