Investigating and Modeling the Acoustic Release of Doxorubicin from Folate Targeted Micelles

Abstract

To minimize the adverse side effects of conventional chemotherapy, a targeted micellar drug carrier was investigated that retains hydrophobic drugs in its core and then releases the drug via ultrasound. This thesis reports the synthesis of Pluronic P105 micelles with folic acid conjugated to their surface and measures the percent drug release from folated versus non-folated micelles at 70 kHz and different acoustic power densities. The encapsulated drug is Doxorubicin (Dox). Two physical models and their corresponding mathematical representation are then used to fit the data. The zero-order release with first-order re-encapsulation showed the best fit to the kinetic data of this targeted micellar system. Additionally, the acoustic activation power density and Gibbs free energy were calculated for folated and non-targeted micelles. An artificial neural network (ANN) model is also developed in an attempt to model the dynamic release of Dox from both folated and non-folated micelles and its subsequent re-encapsulation under various ultrasonic power densities at 70 kHz. The analysis shows that folated micelles exhibit a higher percentage of ultrasonic drug release than non-folated micelles. This could be because the folic acid ligand compromises the structural integrity of the micelle. Furthermore, the data suggest an important role of transient cavitation in drug release due to the presence of a power density threshold.