Liver‐targeting doxorubicin‐conjugated polymeric prodrug with pH‐triggered drug release profile |
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| Authors: | Jin Huang Feng Gao Xiaoxin Tang Jiahui Yu Daxin Wang Shiyuan Liu Yaping Li |
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| Affiliation: | 1. Institute for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, PR China;2. College of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China;3. Subei Hospital of Jiangsu Province, Yangzhou University, Yangzhou 225001, PR China;4. Department of Diagnostic Imaging, Changzheng Hospital, Shanghai 200003, PR China;5. Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China |
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| Abstract: | The aim of the research presented was to develop a potential liver‐targeting prolonged‐circulation polymeric prodrug of doxorubicin (Dox) with a pH‐triggered drug release profile. In particular, linear dendritic block copolymers composed of polyamidoamine dendrimer (PAMAM) and poly(ethylene glycol) (PEG; number‐average molecular weight of 2000 g mol?1) with or without galactose (Gal) were synthesized. Dox was coupled to the copolymers via an acid‐labile hydrazone linker. These prodrugs, designated Gal‐PEG‐b‐PAMAM‐Doxn and mPEG‐b‐PAMAM‐Doxm, showed accelerated Dox release as the pH decreased from 8.0 to 5.6. Cytotoxicity of the prodrugs was lower than that of free Dox due to the gradual drug release nature. Compared to mPEG‐b‐PAMAM‐Doxm, Gal‐PEG‐b‐PAMAM‐Doxn showed rather high cytotoxicity against Bel‐7402, suggestive of its galactose receptor‐mediated enhanced tumor uptake. This galactose receptor‐mediated liver‐targeted profile was further confirmed by the prolonged retention time in hepatoma tissue monitored using magnetic resonance imaging. Gal‐PEG‐b‐PAMAM‐Doxn showed better in vivo antitumor efficacy than free Dox, suggesting its great potential as a polymeric antitumor prodrug. Copyright © 2010 Society of Chemical Industry |
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| Keywords: | Gal‐PEG‐b‐PAMAM‐Doxn polymeric prodrug pH‐triggered drug release doxorubicin liver‐targeting |
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