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

The effect of Pluronic P-105 micelle structure and ultrasound on the uptake of two anthracycline drugs, doxorubicin and its paramagnetic analogue, rub oxyl, by HL-60 cells was investigated. Pluronic micellization was studied o ver the temperature range of 25-42 degrees C using the EPR and fluorescence spectroscopy. In the presence of Pluronic P-105 at concentrations correspo nding to unimers (or loose aggregates), drug uptake by HL-60 cells was enha nced, apparently due to the effect of the polymeric surfactant on cell memb rane permeability. At Pluronic concentrations corresponding to the formatio n of dense micelles with hydrophobic cores, drug uptake was substantially d ecreased. However, insonation with 70 kHz ultrasound enhanced the intracell ular uptake of drugs encapsulated in dense Pluronic micelles. These finding s may provide for developing a new technique of drug targeting by encapsula ting the drug in micelles to prevent unwanted interactions with healthy cel ls and focusing ultrasound on a tumor to enhance drug uptake at the tumor s ite. (C) 1999 Elsevier Science B.V. All rights reserved.