Release of Doxorubicin from Unstabilized and Stabilized Micelles Under the Action of Ultrasound

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Abstract
Polymeric micelles are being investigated as chemotherapy drug delivery carriers using ultrasound as a trigger mechanism. The aim of this paper is to measure the release of Doxorubicin (Dox) from the core of unstabilized Pluronic P105 micelles, Pluronic P105 micelles stabilized with an interpenetrating network of N,N-diethylacrylamide, and micelles of poly(ethylene oxide)-b-poly (N-isopropylacrylamide)-b-poly(oligolactylmethacrylate) with stabilized cores. An ultrasonic exposure chamber with fluorescence detection was used to measure the release of the antineoplastic agent from both stabilized and unstabilized micelles. The release of Dox at 37 °C from unstabilized Pluronic appears to be several times higher than release from the more stabilized and crosslinked copolymers at the same temperature. Although there is a difference in the amount of release between the different compounds, the onset of release occurs at about the same ultrasonic power density for all carriers investigated in this study. The threshold of drug release for all the compounds correlates to the emergence of subharmonic peaks detected in the acoustic spectra. We hypothesize that shearing events caused by cavitating bubbles play an important role in the acoustically activated release of chemotherapy agents delivered from various polymeric drug delivery vehicles.