Optimizing the therapeutic efficacy of cisplatin PEGylated liposomes via incorporation of different DPPG ratios: In vitro and in vivo studies.

The anionic lipid DPPG is known to enhance the cellular uptake of liposomes by forming phase boundaries of high fusogenic potentials in vesicular membranes. The focus of this study is to optimize DPPG concentrations to improve the therapeutic efficacy of cisplatin-loaded liposomes. First, cisplatin liposomes composed of HSPC, mPEG2000-DSPE and cholesterol with increasing amounts of DPPG (10, 20 and 30% mol) were prepared by ethanol injection. Liposomes were then characterized by their size, zeta potential and cytotoxicity against C26 colon carcinoma cells. In an experimental system, based upon C26 tumor bearing BALB/c, mice were treated with administering i.v. doses of different formulations, once weekly for total of three weeks. Although with the highest DPPG ratio (30% mol) liposomes exhibited the highest toxicity in vitro, at 10% DPPG better stability of the encapsulated drug was obtained in the presence of serum. In addition, survival of animals was substantially improved at 10% DPPG compared to the higher DPPG contents. It is thus presumable that the high density of negatively charged residues of DPPG gave rise to repulsive forces between phospholipids in concentric lipid bilayers, which resulted in the instability of lipid structure and the subsequent premature drug leakage. Results indicated that cisplatin liposome fabricated with the inclusion of 10% DPPG, maintains the stability while in circulation, and improves therapeutic efficacy due to fusogenic properties; therefore might serve as an effective and stable formulation of cisplatin. However, further investigations are required to confirm the potential anti-tumor effects of cisplatin anionic nanoliposomes in various tumor types.