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Water-soluble Withaferin A polymer prodrugs via a drug-functionalized RAFT CTA approach

Tijdschriftbijdrage - Tijdschriftartikel

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.
Tijdschrift: European Polymer Journal
ISSN: 0014-3057
Volume: 110
Pagina's: 313 - 318
Jaar van publicatie:2019