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Preparation of a Camptothecin Prodrug with Glutathione‐Responsive Disulfide Linker for Anticancer Drug Delivery
Author(s) -
Xu Zhigang,
Wang Dongdong,
Xu Shuang,
Liu Xiaoyan,
Zhang Xiaoyu,
Zhang Haixia
Publication year - 2014
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201301030
Subject(s) - prodrug , camptothecin , chemistry , glutathione , doxorubicin , linker , cytotoxicity , drug delivery , pharmacology , polyethylene glycol , drug , in vitro , combinatorial chemistry , biochemistry , organic chemistry , chemotherapy , enzyme , medicine , surgery , computer science , operating system
We present here a novel camptothecin (CPT) prodrug based on polyethylene glycol monomethyl ether‐ block ‐poly(2‐methacryl ester hydroxyethyl disulfide‐ graft ‐CPT) (MPEG‐SS‐PCPT). It formed biocompatible nanoparticles (NPs) with diameters of approximately 122 nm with a CPT loading content as high as approximately 25 wt % in aqueous solution. In in vitro release studies, these MPEG‐SS‐PCPT NPs could undergo triggered disassembly and much faster release of CPT under glutathione (GSH) stimulus than in the absence of GSH. The CPT prodrug had high antitumor activity, and another anticancer drug, doxorubicin hydrochloride (DOX ⋅ HCl), could also be introduced into the prodrug with a high loading amount. The DOX ⋅ HCl‐loaded CPT prodrug could deliver two anticancer drugs at the same time to produce a collaborative cytotoxicity toward cancer cells, which suggested that this GSH‐responsive NP system might become a promising carrier to improve drug‐delivery efficacy.