Sequestration and Ultrasound-Induced Release of Doxorubicin from Stabilized Pluronic P105 Micelles

Controlled drug delivery from micelles requires that the micelles remain stable when diluted below their critical micelle concentration, such as upon injection into blood. A cross-linked, interpenetrating network of N,N-diethylacrylamide (NNDEA) was polymerized in the core of Pluronic P105 micelles to stabilize temporarily the micelles at concentrations below the critical micellar concentration of free P105. The stabilized Pluronic micelles (called Plurogels) were able to sequester the drug doxorubicin (Dox) and protect HL-60 cells from the drug at concentrations where non-stabilized Pluronic provided no protection. The protection lasted ~ 12 hr, which is similar to the half-life of the particles. Application of low-frequency ultrasound resulted in a synergistic killing effect with Dox and low concentrations of either Pluronic P105 or stabilized Plurogels, most probably due to release of Dox and permeabilization of the cell membrane.