pH-sensitive PEG-based micelles for tumor targeting.

A new acid sensitive nanocarrier based on lipid core micelles has been investigated for tumor targeted drug delivery. Sulfadimethoxine-PEG-phospholipid unimer (SD-PEG-DSPE) was designed to endow micelles with pH responsiveness in the physiopathologic range. The unimer was synthesized according to a two-step procedure. Potentiometric analysis showed that SD-PEG-DSPE has pK(a) of 6.7. In water, the unimers assembled spontaneously in 20 nm size micelles with 60 μM critical micelle concentration. The particle size was not affected by the pH in the 6.2-7.4 range. The micelles loaded paclitaxel very efficiently and released the drug slowly regardless the incubation pH. Fluorescence spectroscopy and cytofluorimetry carried out by MCF7 tumor cell incubation with labeled SD-PEG-DSPE micelles at pH 7.4 and 6.2 showed that micelles associate with cells mostly at acidic pH with a time-dependent behavior. A cell subpopulation took up the nanocarrier more efficiently at pH 6.2. Confocal microscopy confirmed that under these conditions the systems are taken up by cells or fuse with cellular membrane. Cytotoxicity studies demonstrated that the SD-PEG-DSPE micelles deliver more efficiently paclitaxel at pH 6.2 than at neutral pH confirming that the cell internalization can be triggered by the external environmental conditions.