Improved cellular uptake, enhanced efficacy and promising pharmacokinetic profile of docetaxel employing glycine-tethered C60-fullerenes.

ABSTRACT

Water dispersible fullerenes were synthesized by tethering with glycine. The glycinated fullerenes were conjugated to docetaxel and characterized using FT-IR and NMR. The nanometric drug-loaded carriers were able to release drug at cancer cell pH, but resisted drug release at plasma pH. The cytotoxicity in MDA MB-231 cells was substantially enhanced as well as the system was well tolerated by erythrocytes. The confocal laser scanning microphotographs confirmed the substantial drug delivery to cytosol as well as nuclei of cancer cells. The developed system not only increased the circulation time of drug, but also decreased its protein binding and substantially enhanced AUC. The glycinated fullerenes can serve as promising "cargo vehicles" for delivery of anti-cancer drugs in safe and effective manner.