Improving plasma stability and antitumor effect of gemcitabine via PEGylated liposome prepared by active drug loading

Abstract

Gemcitabine, as a nucleoside analog, has been used as first-line chemotherapy drug for many years. However, the treatment dose of gemcitabine in the clinic has been usually extremely high due to its rapid metabolism. The aim of this study was to achieve successful chemotherapy at low doses by a PEGylated liposomal delivery system. The liposomes were prepared with Lipoid S-100, Cholesterol and DSPE-PEG2000 (at a molar ratio of 9:2:0.07) by the film dispersion-extrusion-ammonium sulfate gradient method. The entrapment efficiency (EE, %) and drug loading (DL, %) of the liposomes (117.8 ± 16.85 nm) were 68.83% and 2.52%, respectively. The in vitro release study and plasma stability experiments showed the gemcitabine liposomes (GEM-Lip) was more stable than gemcitabine solutions (GEM-Sol) at pH 7.4 and in the plasma. AUC and Cmax of GEM-Lip were shown to be 6.20 and 16.44-fold higher than that of the solutions. The pharmacodynamics (PD) experiment in Kunming mice bearing a H22 cancer cell model showed that the tumor inhibition rate (TIR) of GEM-Lip was 6.25-fold as that of GEM-Sol when administrated intravenously. Our findings demonstrated that the preparation of GEM-Lip could effectively enhance the pharmacokinetic properties, the plasma stability and antitumor effect of gemcitabine.