Synthesis and self-assembly of a novel block copolymer poly(N-vinylcaprolactam)-b-poly(3- hydroxybutyrate-co-3-hydroxyvalerate) (PNVCL-b-PHBHV) by the combination of RAFT/MADIX and click chemistry techniques

Amphiphilic copolymers have gained significant attention in the field of drug delivery systems (DDS). The key feature that makes them promising for such application is their ability to self-assemble into micelles in aqueous media. In this context, this work describes the synthesis of a novel amphiphilic well-defined block copolymer, poly( N -vinylcaprolactam)- b -poly(3-hydroxybutyrate- co -3-hydroxyvalerate) (PNVCL- b -PHBHV), using a strategy that combines reversible addition-fragmentation chain-transfer macromolecular design via interchange of xanthates (RAFT/MADIX) polymerization and click chemistry reaction. Initially, azido-terminated PNVCL homopolymers (PNVCL-N ₃ ) were synthesized through RAFT/MADIX polymerization of the N -vinylcaprolactam (NVCL) monomer, mediated by a chain transfer agent (CTA) bearing an azide group. Meanwhile, the alkyne-terminated PHBHV (alkyne-PHBHV) was prepared by the transesterification reaction between PHBHV and propargyl alcohol. Then, the 1,3-cyclo addition reaction between azide and alkyne (CuAAC) was used to obtain the block copolymer PNVCL- b -PHBHV. Different size chains of PHBHV were evaluated as also their influence on the capacity of micelles formation. The chemical structures of all (co)polymers were assessed by Fourier-Transform Infrared spectroscopy (FTIR) and Proton Nuclear Magnetic Resonance spectroscopy ( ¹ H NMR) analysis, while their molar masses were determined by Size Exclusion Chromatography (SEC). Differential Scanning Calorimetry (DSC) measurement showed that the PNVCL- b -PHBHV have lower degree of crystallinity than PHBHV. Additionally, it was observed that the critical micelle concentration (cmc) of the block copolymers in aqueous solution decreased as the length of the hydrophobic block increased, whereas the size of the polymeric micelles grew with a higher proportion of hydrophobic segments.