In this report, a newly liposomal formulation of
paclitaxel (PTX) based on dual
paclitaxel succinate glycerophosphorylcholine (Di-PTX-GPC)
prodrug was developed. The Di-PTX-GPC
prodrug was synthesized by conjugating PTX with GPC through esterification under
N,N'-carbonyldiimidazole (CDI) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) catalytic system. Di-PTX-GPC
liposomes were prepared by thin film method and characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). The results indicated that the
liposomes have an average diameter of 157.9nm with well-defined spherical morphology. In vitro drug release studies confirmed that the Di-PTX-GPC
liposomes have controlled release profile of PTX at a weakly acidic environment, which formulates them suitable for sustained drug delivery. Additionally, in vitro cellular uptake analysis and cytotoxicity evaluation showed that Di-PTX-GPC
liposomes were internalized successfully into
tumor cells to induce the apoptosis against MCF-7, HeLa and HepG-2 cells. In vivo pharmacokinetics study revealed that such liposomal formulation of Di-PTX-GPC has longer retention half-life in bloodstream, which subsequently leads to slight accumulate in
tumor sites due to enhanced permeability and retention (EPR) effect. More importantly, Di-PTX-GPC
liposomes demonstrated good in vivo anticancer activities compared to
Taxol with reduced adverse effects. Conclusively, these results suggest that Di-PTX-GPC
liposomes could be an effective PTX delivery vehicles in clinical
cancer chemotherapy.