Liposomes as multicompartmental carriers for multidrug delivery in anticancer chemotherapy.

Abstract

A new PEGylated liposomal formulation containing both gemcitabine (GEM) and paclitaxel (PTX) was investigated in order to realize an innovative multidrug carrier (MDC) to test on human cancer cells. The MDC in question was realized by the liposome extrusion method. Photocorrelation spectroscopy was used for the physicochemical characterization of the vesicular carriers. In vitro cytotoxicity was studied through MTT testing. The contemporary presence of the two antitumoral compounds induced no destabilization phenomena in the liposomal structure. The extrusion method provided vesicles with mean sizes of ∼100nm and a zeta-potential of ∼ -10mV. The liposomal MDC showed a high drug loading capacity (∼90% and ∼80% for GEM and PTX, respectively) as well as a controlled release of the active compounds over a 24-h period. Cell viability testing on Michigan Cancer Foundation-7 human breast cancer cells evidenced the MDC as having a stronger cytotoxic effect with respect to the active compounds tested in free and liposomal formulations, both as single molecules and in association. Flow cytometry furnished evidence of the synergistic in vitro antitumoral action between the GEM and PTX co-encapsulated the liposomal MDC. This formulation may offer even more advantages in in vivo testing in terms of drug pharmacokinetic, biodistribution, and antitumoral efficacy for the treatment of breast cancer, as compared to past formulations.