Poly(N-vinylpyrrolidone-b-(γ-benzyl-l-glutamate)) – synthesis and self-assembly into pH-sensitive micelles

Abstract

The synthesis of hybrid amphiphilic block copolymers using thiazolidine chemistry is described. The system consists of poly(N-vinylpyrrolidone) (PVP) as the hydrophilic polymer while incorporating a hydrophobic polypeptide, poly(γ-benzyl-L-glutamate) (PBLG), resulting in a pH-sensitive bioconjugate. A modular approach was used for the synthesis of the conjugates. As a first step, the synthesis of well-defined end-functional polymers is described. An optimized procedure was developed to quantitatively obtain ω-aldehyde end-functional PVP as well as one to synthesize cysteine end-functional PBLG. The latter makes use of a modified deprotection step for the thiol-protecting acetamidomethyl group. The self-assembly behaviour and pH dependence of the PVP-PBLG bioconjugate is demonstrated, which indicates the potential of this system as a “smart” drug delivery vehicle.