title: Y-shaped mPEG-PLA cabazitaxel conjugates: well-controlled synthesis by organocatalytic approach and self-assembly into interface drug-loaded core-corona nanoparticles.
abstract: 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.
authors: Université de Toulouse , UPS, LHFA, 118 route de Narbonne, 31062 Toulouse, France.
authors: Fethi
authors: F
authors: Bensaid
authors: Olivier
authors: O
authors: Thillaye du Boullay
authors: Abderrahmane
authors: A
authors: Amgoune
authors: Christian
authors: C
authors: Pradel
authors: L
authors: L
authors: Harivardhan Reddy
authors: Eric
authors: E
authors: Didier
authors: Serge
authors: S
authors: Sablé
authors: Guillaume
authors: G
authors: Louit
authors: Didier
authors: D
authors: Bazile
authors: Didier
authors: D
authors: Bourissou
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D004337:Drug Carriers; D057927:Hydrophobic and Hydrophilic Interactions; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D043823:Taxoids / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D043823:Taxoids; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; C552428:cabazitaxel