High intensity focused ultrasound-responsive release behavior of PLA-b-PEG copolymer micelles

Poly(lactic acid) (PLA) was synthesized by solution polycondensation of L-lactic acid and further reacted with dihydroxyl poly(ethylene glycol) (PEG) to obtain the amphiphilic block copolymer PLA-b-PEG. The biodegradable PLA-b-PEG copolymer can self-assemble into spherical micelles in aqueous solution. Nile Red, as a payload model, was used to examine the release behavior of the micelles. The hydrophobic Nile Red can be adsolubilized into the hydrophobic inner core of PLA-b-PEG micelles. With the introduction of Nile Red, the size of micelles increased. Moreover, high intensity focused ultrasound (HIFU), as a non-contact and remote control approach, was introduced to control the release behavior of PLA-b-PEG micelles containing Nile Red. The release behavior of Nile Red was monitored by fluorescence emission spectra. The results showed that HIFU can trigger the release of the encapsulated Nile Red from PLA-b-PEG micelles. By adjusting the HIFU time, intensity and location, the release behavior of Nile Red from micelles can be tuned. Base on the results, an irreversible release mechanism under HIFU was proposed. The irreversible release of Nile Red from the PLA-b-PEG micelle was attributed to a chemically breaking process of micelle structure due to the degradation of the PLA-b-PEG chain that resulted from the transient cavitation in the HIFU focal spot.