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.