Y‑Shaped mPEG-PLA Cabazitaxel Conjugates: Well-Controlled
Synthesis by Organocatalytic Approach and Self-Assembly into Interface
Drug-Loaded Core–Corona Nanoparticles
Fethi Bensaid
Olivier Thillaye
du Boullay
Abderrahmane Amgoune
Christian Pradel
L. Harivardhan Reddy
Eric Didier
Serge Sablé
Guillaume Louit
Didier Bazile
Didier Bourissou
10.1021/bm400161g.s001
https://acs.figshare.com/articles/journal_contribution/Y_Shaped_mPEG_PLA_Cabazitaxel_Conjugates_Well_Controlled_Synthesis_by_Organocatalytic_Approach_and_Self_Assembly_into_Interface_Drug_Loaded_Core_Corona_Nanoparticles/2426173
A well-defined poly(ethylene glycol)
methyl ether-<i>b</i>-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 D<sub>2</sub>O. 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.
2013-04-08 00:00:00
temperature NMR analysis
nanoparticle
copolymer conjugate
NP
2O
PLA