Poly(β-hydroxyalkanoate)/polymethacrylate self-assembled architectures by ring-opening polymerization (ROP)/reversible addition–fragmentation chain-transfer (RAFT) polymerization and polymerization-induced self-assembly (PISA)†

Abstract

Self-assembled poly(β-hydroxyalkanoate) (PHA)-based block copolymers are attractive materials for biomedical applications due to the biocompatibility and (bio)degradability of the PHA segment. Herein, we report the synthesis and formation of self-assemblies based on PHAs: namely, poly(3-hydroxybutyrate) (PHB) was prepared by ring-opening polymerization (ROP) of racemic β-butyrolactone (rac-β-BL) using a discrete yttrium-based catalyst in the presence of a hydroxy-terminated trithiocarbonate (TTC-OH) as initiator. The resulting TTC end-capped PHB prepolymer next promoted the controlled reversible addition–fragmentation chain-transfer (RAFT) polymerization of 2-hydroxy ethyl methacrylate (HEMA). When performed in THF, in which the initial solvophilic PHB-TTC segment and HEMA monomer are both fully soluble, this second step resulted in a polymerization-induced self-assembly (PISA) leading to the formation of nanoparticles, as the solvophobic PHEMA precipitated in the dispersed medium. The effective extension of the PHB block by a PHEMA segment, as evidenced by SEC and NMR analyses, highlighted the efficiency of the PHB-TTC macro-RAFT agent. This ROP/RAFT/PISA strategy revealed successful at various polyester (DP = 45–90) and polymethacrylate (DP = 200–500) block lengths. The size, polydispersity index (PDI) and morphology of the resulting self-assembled PHB_x-b-PHEMA_y particles were assessed by dynamic light scattering (DLS) measurements, transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS). Depending on both segments chain-lengths, DLS enabled identifying particles in suspension having hydrodynamic diameters (D_H) varying from 56 to 194 nm, with narrow polydispersity index, i.e. PDI < 0.140. SAXS measurements and TEM observations revealed vesicles morphology for specific PHB_x-b-PHEMA_y samples presenting apparent diameters ranging from 134 to 316 nm. These morphologies support the successful copolymerization through a PISA process, first reported herein for the elaboration of PHA-based objects that may be valuable nano-vehicles of active ingredients for biomedical applications.