Cancer chemotherapeutic systems with high antitumor effects and less adverse effects are eagerly desired. Here, a pH-sensitive delivery system for
bleomycin (BLM) was developed using egg yolk
phosphatidylcholine liposomes modified with poly(
ethylene glycol)-
lipid (
PEG-PE) for long circulation in the bloodstream and 2-carboxycyclohexane-1-carboxylated
polyglycidol-having distearoyl
phosphatidylethanolamine (CHexPG-PE) for pH sensitization. The
PEG-PE/CHexPG-PE-introduced
liposomes showed content release responding to pH decrease and were taken up by
tumor cells at a rate 2.5 times higher than that of
liposomes without CHexPG-PE. BLM-loaded
PEG-PE/CHexPG-PE-introduced
liposomes exhibited comparable cytotoxicity with that of the free drug.
Intravenous administration of these
liposomes suppressed
tumor growth more effectively in
tumor-bearing mice than did the free drug and
liposomes without CHexPG-PE. However, at a high dosage of BLM, these
liposomes showed severe toxicity to the spleen, liver, and lungs, indicating the trapping of
liposomes by mononuclear phagocyte systems, probably because of recognition of the carboxylates on the
liposomes. An increase in PEG molecular weight on the
liposome surface significantly decreased toxicity to the liver and spleen, although toxicity to the lungs remained. Further improvements such as the optimization of PEG density and
lipid composition and the introduction of targeting
ligands to the
liposomes are required to increase
therapeutic effects and to reduce adverse effects.