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

Abstract

Amphiphilic copolymers have attracted considerable attention in the field of drug delivery systems (DDS) due to their ability to self-assemble into micelles in aqueous media. In this study, we report the synthesis of a novel amphiphilic, well-defined block copolymer, poly(N-vinylcaprolactam)-b-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PNVCL-b-PHBHV), via a combined approach using reversible addition–fragmentation chain transfer–macromolecular design via interchange of xanthates (RAFT/MADIX) polymerization and click chemistry reaction. Initially, azide-terminated PNVCL homopolymer (PNVCL-N₃) was synthesized through RAFT/MADIX polymerization of the N-vinylcaprolactam (NVCL) monomer, mediated by a chain transfer agent (CTA) bearing an azide group. Concurrently, the alkyne-terminated PHBHV (alkyne-PHBHV) was prepared by the transesterification reaction between PHBHV and propargyl alcohol. Subsequently, the 1,3-dipolar cycloaddition reaction between azide and alkyne (Copper(I)-catalyzed Azide–Alkyne Cycloaddition—CuAAC) was used to obtain the block copolymer PNVCL-b-PHBHV. The influence of PHBHV chain lengths on micelle formation capacity was evaluated. The chemical structures of all (co)polymers were assessed by Fourier-Transform Infrared spectroscopy (FTIR) and Proton Nuclear Magnetic Resonance spectroscopy (¹H NMR), while their molar masses were determined by Size Exclusion Chromatography (SEC). Differential Scanning Calorimetry (DSC) measurements showed that the PNVCL-b-PHBHV has lower degree of crystallinity compared to 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.