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