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Y‑Shaped mPEG-PLA Cabazitaxel Conjugates: Well-Controlled Synthesis by Organocatalytic Approach and Self-Assembly into Interface Drug-Loaded Core–Corona Nanoparticles

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journal contribution
posted on 08.04.2013, 00:00 by Fethi Bensaid, Olivier Thillaye du Boullay, Abderrahmane Amgoune, Christian Pradel, L. Harivardhan Reddy, Eric Didier, Serge Sablé, Guillaume Louit, Didier Bazile, Didier Bourissou
A well-defined poly­(ethylene glycol) methyl ether-b-poly­(lactic acid) copolymer (mPEG-PLA) featuring a new, Y-shaped, architecture with a hydroxyl functional group between the two blocks has been prepared and thoroughly characterized. The functional copolymer was then readily coupled to diglycolyl-cabazitaxel. The resulting copolymer conjugates assembled into stable and monodisperse nanoparticles (NPs) in aqueous suspension. The architecture of the copolymer conjugate is shown to impact the spatial distribution of the drug within the nanoparticles. With the Y-shaped architecture, cabazitaxel was found localized at the interface of the hydrophobic PLA core and the hydrophilic mPEG corona of the NPs, as substantiated by variable temperature NMR analysis of the nanoparticles in D2O. Preliminary in vitro release studies reveal dependence on the architecture of the copolymer conjugate. This new approach offers promising perspectives to finely tune the position of the active ingredient in polymeric nanoparticles.