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Bleomycin-LoadedpH-SensitivePolymer–Lipid-Incorporated Liposomes forCancer Chemotherapy Eiji YubaTomohiro OsakiMisato Ono2018 год

Bleomycin-Loaded pH-Sensitive Polymer–Lipid-Incorporated Liposomes for Cancer Chemotherapy
статья из журнала

Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: 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.
Год издания: 2018
Авторы: Eiji Yuba, Tomohiro Osaki, Misato Ono, Shinjae Park, Atsushi Harada, Masamichi Yamashita, Kazuo Azuma, Takeshi Tsuka, Norihiko Ito, Tomohiro Imagawa, Yoshiharu Okamoto
Издательство: Multidisciplinary Digital Publishing Institute
Источник: Polymers
Ключевые слова: Nanoparticle-Based Drug Delivery, RNA Interference and Gene Delivery, Nanoplatforms for cancer theranostics
Другие ссылки: Polymers (PDF)
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Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)