CBABC terpolymer-based nanostructured vesicles with tunable membrane permeability as potential hydrophilic drug nanocarriers

Abstract

The self-assembly of an amphiphilic pentablock terpolymer, consisting of a pH-sensitive poly(2-vinylpyridine) (P2VP) central block, bearing at both ends hydrophilic poly(ethylene oxide) (PEO) end-capped with hydrophobic poly(ε-caprolactone) (PCL) blocks was investigated in aqueous media. When the polymer was transferred to aqueous medium through solvent exchange technique, micellar assemblies were obtained, with a morphological switch from “flower-like” crew-cut micelles to large compound vesicles upon partial quaternization of 2VP block. More importantly, well-defined polymer vesicles were formed when thin film hydration method was employed. Such polymersomes presented “flower-like” morphology, with a membrane composed of self-assembled P2VP hydrophobic central blocks shielded by PCL hydrophobic ends and surrounded by PEO looping chains at the inner and outer surfaces. The potential of the pentablock vesicles as drug delivery carriers was explored by encapsulation of calcein, a model hydrophilic drug, in the polymersomes and monitoring its release at different pH values simulating physiological environments. It is shown that the release profile of the nanoparticle formulations could be modulated by tuning the membrane permeability either through chemical (i.e. partial quaternization) and/or physical (i.e. pH variations) pathways.