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Title
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Water-soluble withaferin A polymer prodrugs via a drug-functionalized RAFT CTA approach
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Author
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Abstract
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| To cope with the poor aqueous solubility of withaferin A, a broad-spectrum anti-cancer agent effective against therapy-resistant cancers, a polymer-drug conjugate was synthesized via a grafting-from-drug approach. Modification of withaferin A at the C27-OH with a chain transfer agent (CTA) for reversible addition-fragmentation chain transfer (RAFT) polymerization through a degradable ester bond was achieved with excellent control on the regioselectivity via a PFP-ester transesterification route. Subsequent RAFT polymerization with the hydrophilic N,N-dimethylacrylamide yielded a fully water-soluble conjugate. A decreased cytotoxicity in vitro indicated that withaferin A exists as a prodrug in the conjugate form and requires hydrolysis of the ester to regain its activity. |
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Language
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English
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Source (journal)
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European polymer journal. - Oxford
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Publication
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Oxford
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2019
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ISSN
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0014-3057
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Volume/pages
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110
(2019)
, p. 313-318
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ISI
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000456751000038
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Full text (Publisher's DOI)
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Full text (open access)
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Full text (publisher's version - intranet only)
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