Ultrasound-Induced Cavitation for Controlled Drug Release from Thermosensitive Liposomes
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Ultrasound-induced cavitation of microbubbles has increased anticancer drug Doxorubicin (DOX) release from thermosensitive liposomes (TSL). Yet, the influence of liposomal formulations and their responses toward cavitation on controlled drug release of TSL is inadequately investigated. This novel research evaluates the contribution of heating and cavitation in enhancing drug release of biotinylated, doxorubicin-loaded thermosensitive liposomes (TSL-DOX) by changing liposomal formulations and ultrasound conditions. We have found that combining heating and cavitation triggers the maximum cumulative DOX release (80%~100%) than heating or cavitation only. The final cumulative drug release percentages are mainly dependent on the membrane compositions, which are influenced by changing the molar ratios of DSPE-PEG2K-biotin. Heating TSL-DOX to the phase transition temperature (Tm : ~ 42 ºC) is the driving force of DOX release (~ 70%). However, when the temperature is below Tm , cavitation can also trigger more DOX release of 10~20%. Cavitation (ultrasound frequency: 1 MHz, 10% duty cycle, 1kHz pulse repetition frequency, and 10 s exposure period) increased more DOX release by 20 ~ 25% after heating at 37 ºC and 42 ºC. Without cavitation, changing ultrasound parameters: burst cycles and exposure periods slightly influenced DOX release. Interestingly, increasing the molar ratios of DSPE-PEG2K-biotin decreased DOX release% even treating with cavitation and heating. To further evaluate the influence of cavitation on TSL-DOX, we also developed liposome-conjugated microbubbles (TSL-MB) via biotin-avidin-biotin linkage. DiO-labeled TSLDOX have been shown to conjugate to the surface of DiD-labeled microbubbles. After treating with heating and cavitation, TSL-MB improved DOX release within 5 min of heating, compared to TSLDOX. In summary, we successfully proved that combining cavitation and heating can improve drug release, and heating to T m is the major incentive to control drug release. These findings would support the development of novel liposomal drug control-release methods using both cavitation and heating.
Cite this version of the work
Anni Pan (2022). Ultrasound-Induced Cavitation for Controlled Drug Release from Thermosensitive Liposomes. UWSpace. http://hdl.handle.net/10012/18211