Short-Term Comparative Study of the Cyclophosphamide Genotoxicity Administered Free and Liposome-Encapsulated in Mice

BACKGROUND: Cyclophosphamide (CYP) is used to treat a wide range of human tumors. However, the mutagenic effect of CYP is still the primary limitation for wider applications to treat a variety of human malignancies. It has been reported that CYP entrapped in liposomes reduces non-specific toxicity and enhances anticancer effects in animal systems. METHODS: In the present experiment, mice were injected with 50 mg/kg free CYP or encapsulated in liposomes to compare their ability to induce mutagenic damages including chromosomal aberrations, changes in Sister Chromatid Exchange (SCEs) frequencies, and in Mitotic Index (MI), as well as in cell cycle kinetics. RESULTS: Both forms of CYP induced an increase in chromosomal aberrations and SCEs at the different sampling time. On the contrary, a decrease in mitotic index and delay in cell cycle kinetics was observed at all stages of the experiment. CONCLUSION: Encapsulation of CYP increased its mutagenicity, especially at a longer sampling time. This may due to interaction of liposomes with cells which is mainly through endocytosis or fusion resulting in accumulation of drug inside the cell causing chromosomal damage. Further evaluation of possible toxicity of encapsulation drugs in healthy tissue is needed.