Synthesis of functionalized Pluronic-b-poly(ε-caprolactone) and the comparative study of their pendant groups on the cellular internalization behavior

This study focuses on the synthesis of Pluronic- b -poly( ε -caprolactone) bearing benzyl-oxycarbonylmethyl and carboxylic groups and the comparative study to investigate the influence of the different pendant groups on the cellular behavior. The functionalized Pluronic- b -poly( ε -caprolactone) bearing two kinds of pendant groups are synthesized via ring-opening polymerization of ε -caprolactone and 6-(benzyl-oxycarbonyl methyl)- ε -caprolactone and followed by deprotection respectively. The structure of the copolymers is confirmed and the polymeric micelles are formed by an emulsion/solvent evaporation technique. The critical micelle concentrations are improved compared with Pluronic F127, the morphologies of the micelles are spherical with the diameter on nano scale and good colloidal stability. The copolymers have good cytocompatibility and the comparative study reveals that cellular internalization, digesting by lysosome and intracellular distribution are affected by the pendant groups, moreover, the endocytosis pathway is determined by the pendant groups. Therefore, the definite internalization mechanism is beneficial for the design of polymeric micellar carriers to achieve intra- or extracellular modes of drug delivery and provide better access to either cell membrane or intracellular organelles.