One-pot self-assembly directed fabrication of biocompatible core cross-linked polymeric micelles as a drug delivery system

Abstract

A series of pH-responsive diblock copolymers, methoxy poly(ethylene glycol)-poly(2-(diethylamino)ethyl methacrylate) (mPEG-PDEA), were synthesized via the atom transfer radical polymerization (ATRP) technique based on the poly(ethylene glycol) (PEG)-macroinitiator. The obtained diblock copolymers exhibit interesting micellization behavior in aqueous solution, and self-assemble into core–shell micelles by adjusting the solution pH at ambient temperature. In both cases, transmittance and transmission electron microscopy (TEM) reveal the presence of the near-monodispersed micelles. Novel core cross-linked (CCL) micelles with pH-responsive PDEA cores and biocompatible PEG coronas were fabricated with a one-pot self-assembly directed synthesis approach with N,N′-methylene bisacrylamide as the cross-linker in methanol at 60 °C. The reversible pH-dependent swelling–shrinking of the PDEA cores of the obtained CCL micelles was investigated in detail by DLS and TEM. As the structurally stable pH-induced CCL micelles have been exploited to develop a solvent-free protocol for drug loading, the release profile of model hydrophobic drugs, dipyridamole (DIP), ibuprofen and famotidine, initially loaded within the hydrophobic PDEA core via hydrogen bonding, can be controlled by the solution pH. Experiments on controlled release demonstrated that the pH-responsive CCL micelles have a potential application in fields such as drug delivery and smart release.