RESUMEN
This paper studies the thermodynamic characteristics of ultrasound-activated release of Doxorubicin (Dox) from micelles. The release and re-encapsulation of Dox into Pluronic® P105 micelles was measured by recording the fluorescence of a solution of 10 µg/ml Dox and 10% wt P105 polymer in phosphate-buffered saline, during and after insonation by ultrasound at three temperatures, (25 °C, 37 °C and 56 °C). The experimental data were modeled using a previously-published model of the kinetics of the system. The model was simplified by the experimental measurement of one of the parameters, the maximum amount of Dox that can be loaded into the poly(propyleneoxide) cores of the micelles, which was found to be 89 mg/ml PPO and 150 mg Dox/ml PPO at 25 °C and 37 °C, respectively. From the kinetic constants and drug distribution parameters, we deduced the thermodynamic activation energy for micelle re-assembly and the residual activation energies for micelle destruction. Our model showed that the residual activation energy for destruction decreased with increasing acoustic intensity. In addition, higher temperatures were found to encourage micelle destruction and hinder micelle re-assembly.
RESUMEN
The kinetics of the release of Doxorubicin from Pluronic P105 micelles during ultrasonication and its subsequent re-encapsulation upon cessation of insonation were investigated. Four mechanisms are proposed to explain the acoustically-triggered Doxorubicin (Dox) release and re-encapsulation from Pluronic P105 micelles. The four mechanisms are: micelle destruction; destruction of cavitating nuclei; reassembly of micelles, and the re-encapsulation of Dox. The first mechanism, the destruction of micelles during insonation, causes the release of Dox into solution. The micelles are destroyed because of cavitation events produced by collapsing nuclei, or bubbles in the insonated solution. The second mechanism, the slow destruction of cavitating nuclei, results in a slow partial recovery phase, when a small amount of Dox is re-encapsulated. The third and fourth mechanisms, the reassembly of micelles and the re-encapsulatin of Dox, are independent of ultrasound. These two mechanism are responsible for maintaining the drug release at a partial level, and for recovery after insonation ceases. A normal distribution was used to describe micellar size. Parameters for the model were determined based upon the best observed fit to experimental data. The resulting model provides a good approximation to experimental data for the release of Dox from Pluronic P105 micelles.
