Poly(γ-glutamic acid)-coated lipoplexes loaded with Doxorubicin for enhancing the antitumor activity against liver tumors

The study was to develop poly-gamma-glutamic acid (gamma-PGA)-coated Doxorubicin (Dox) lipoplexes that enhance the antitumor activity against liver tumors. gamma-PGA-coated lipoplexes were performed by electrostatistically attracting to the surface of cationic charge liposomes with anionic gamma-PGA. With the increasing of gamma-PGA concentration, the particle size of gamma-PGA-coated Dox lipoplexes slightly increased, the zeta potential from positive shifted to negative, and the entrapment efficiency (EE) were no significant change. The release rate of gamma-PGA-coated Dox lipoplexes slightly increased at acidic pH, the accelerated Dox release might be attributed to greater drug delivery to tumor cells, resulting in a higher antitumor activity. Especially, gamma-PGA-coated Dox lipoplexes exhibited higher cellular uptake, significant in vitro cytotoxicity in HepG2 cells, and improved in vivo antitumor efficacy toward HepG2 hepatoma-xenografted nude models in comparison with Dox liposomes and free Dox solution. In addition, the analysis results via flow cytometry showed that gamma-PGA-coated Dox lipoplexes induce S phase cell cycle arrest and significantly increased apoptosis rate of HepG2 cells. In conclusion, the presence of gamma-PGA on the surface of Dox lipoplexes enhanced antitumor effects of liver tumors.