Ultrasound-Triggered Drug Release and Enhanced Anticancer Effect of Doxorubicin-Loaded Poly(D,L-Lactide-Co-Glycolide)-Methoxy-Poly(Ethylene Glycol) Nanodroplets

Abstract A novel ultrasound-responsive doxorubicin (DOX)–loaded nanoparticulate system was prepared in this study. The DOX-loaded polymeric micelles were first prepared using poly(D,L-lactide-co-glycolide)-methoxy-poly(ethylene glycol) (PLGA-mPEG) with a high encapsulation efficiency of 89.2%. After filling with perfluoropentane (boiling point 29°C), the micelles were transformed into nanodroplets that were stable as a result of the PEG shell. The nanodroplets were transformed into nanobubbles at 37°C, and little drug was released if no ultrasound was exerted. Ultrasound-triggered drug release, with pH dependency, was shown. The DOX release percentage was 9.59% at pH 6.5 (also appeared in tumor) and only 2.22% at pH 7.4 after sonicating for 0.5 min at 37°C. The tumor inhibitory rate of Group III (DOX-loaded nanodroplets combined with ultrasound) was 84.3%, more than that of Group II (DOX-loaded nanodroplets), which was 60.4%. Moreover, the nanodroplets showed much lower toxicity than free drugs. The novel nanodroplets could be a promising anticancer drug delivery system.