Preparation of well-defined ibuprofen prodrug micelles by RAFT polymerization.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat acute pain, fever, and inflammation and are being explored in a new indication in cancer. Side effects associated with long-term use of NSAIDs such as gastrointestinal damage and elevated risk of stroke, however, can limit their use and exploration in new indications. Here we report a facile method to prepare well-defined amphiphilic diblock copolymer NSAID prodrugs by direct reversible addition-fragmentation transfer (RAFT) polymerization of the acrylamide derivative of ibuprofen (IBU), a widely used NSAID. The synthesis and self-assembling behavior of amphiphilic diblock copolymers (PEG-PIBU) having a hydrophilic poly(ethylene glycol) block and a hydrophobic IBU-bearing prodrug block were investigated. Release profiles of IBU from the micelles by hydrolysis were evaluated. Furthermore, the antiproliferative action of the IBU-containing micelles in human cervical carcinoma (HeLa) and murine melanoma (B16-F10) cells was assessed.
Institute of Bioengineering and Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Urara
U
Hasegawa
André J
AJ
van der Vlies
Christine
C
Wandrey
Jeffrey A
JA
Hubbell
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology; D055162:Biocatalysis; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D007052:Ibuprofen / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008823:Micelles; D058726:Nanoconjugates / Q000737:chemistry*; D058105:Polymerization; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D008823:Micelles; D058726:Nanoconjugates; D011355:Prodrugs; D007052:Ibuprofen