Gemcitabine-loaded RGD modified liposome for ovarian cancer: preparation, characterization and pharmacodynamic studies

Zhongyuan Tang, Weiwei Feng, Yiqing Yang, Qun Wang Department of Obstetrics & Gynecology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Weiwei FengDepartment of Obstetrics & Gynecology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, People’s Republic of ChinaTel +86 21 64370045Email fww12066@rjh.com.cnBackground: Ovarian cancer is the third leading cause of death among gynecological cancers in women in China. Chemotherapy is an important method for comprehensive treatment of ovarian cancer, but the curative effect is poor.Purpose: In this study, gemcitabine (GEM) -loaded RGD modified liposomes (LPs) were developed by the emulsification-solvent evaporation method and evaluated for their antitumor activity in vitro and in vivo.Methods: The physicochemical properties of LPs such as particle size, zeta potential and in vitro drug release were investigated. We also demonstrated the effect of RGD-GEM-PEG LPs in ovarian cancer.Results: RGD-PEG3500-DSPE GEM LPs had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 106.7 nm and 0.13 respectively. The ER% and DL% of the formulation were 79.6±3.1% and 6.1±1.4% respectively. Compared with the free drug, RGD modified GEM LPs had sustained-release properties in vitro. In vivo, compared with the DiD-RGD-PEG3500-DSPE GEM LPs group, free DiD-GEM and DiD-GEM LPs had no obvious fluorescence intensity in tumor of mice at all times, indicating that ordinary liposomes and drugs had no tumor targeting function. RGD-PEG3500-DSPE GEM LPs showed a superior antiproliferative effect on SKOV3 cells and had a better antitumor effect in vivo than non-modified LPs.Conclusion: These results indicated that RGD-PEG3500-DSPE GEM LPs were a promising candidate for antitumor drug delivery.Keywords: RGD, gemcitabine, liposomes, sustained-release, antitumor