Micellar delivery of doxorubicin and its paramagnetic analog, ruboxyl, to HL-60 cells: effect of micelle structure and ultrasound on the intracellular drug uptake

Abstract

The effect of Pluronic P-105 micelle structure and ultrasound on the uptake of two anthracycline drugs, doxorubicin and its paramagnetic analogue, ruboxyl, by HL-60 cells was investigated. Pluronic micellization was studied over the temperature range of 25-42 degrees C using the EPR and fluorescence spectroscopy. In the presence of Pluronic P-105 at concentrations corresponding to unimers (or loose aggregates), drug uptake by HL-60 cells was enhanced, apparently due to the effect of the polymeric surfactant on cell membrane permeability. At Pluronic concentrations corresponding to the formation of dense micelles with hydrophobic cores, drug uptake was substantially decreased. However, insonation with 70 kHz ultrasound enhanced the intracellular uptake of drugs encapsulated in dense Pluronic micelles. These findings may provide for developing a new technique of drug targeting by encapsulating the drug in micelles to prevent unwanted interactions with healthy cells and focusing ultrasound on a tumor to enhance drug uptake at the tumor site.