Reduction responsive liposomes based on paclitaxel-ss-lysophospholipid with high drug loading for intracellular delivery.

In this report, a novel redox-responsive liposomes based on disulfide derivative paclitaxel-ss-lysophosphatidylcholine prodrug (PTX-ss-PC) with high PTX loading was developed for triggering drug release. First of all, PTX-ss-PC was synthesized by a facile esterification and verified by MS, 1H NMR and HPLC. After that, PTX-ss-PC derived liposomes (PTX-ss-PC liposomes) containing EPC:Chol:mPEG2000-DSPE components were prepared by the conventional film method. Moreover, physicochemical characterizations of the PTX-ss-PC liposomes were carried out by using transmission electron microscope (TEM), dynamic light scattering (DLS) and release test. It was demonstrated that the PTX-ss-PC liposomes possessed average diameter of 234.9 nm and zeta potential of -29.1 mV with highest PTX loading 7.97%. The PTX-ss-PC liposomes dissociated rapidly in a reduction medium, as confirmed by their triggered aggregation/disruption and rapid release of PTX in the presence of glutathione (GSH). Finally, in vitro cytotoxicity of the liposomes was checked against MCF-7 and A549 cells. It was found that the PTX-ss-PC liposomes exhibited favorable GSH-mediated anti-proliferative activity in comparison with the nonresponsive counterpart. Taken together, the novel PTX-ss-PC based liposomes possess improved loading capacity, reduction triggered release of PTX and efficient anti-proliferative activity, which should be valuable for further preclinical evaluation.