Synthesis of shell cross-linked micelles with pH-responsive cores using ABC triblock copolymers

A series of well-defined poly[(ethylene oxide)-block-2-(dimethylamino)ethyl methacrylate-block-2-(diethylamino) methacrylate] (PEO-DMA-DEA) triblocks were synthesized by successive ATRP polymerization of DMA and DEA monomers using PEO-based macroinitiators of different molecular weights. These triblock copolymers dissolved molecularly in aqueous solution at low pH; on addition of NaOH, micellization occurred at pH 7.1 to form three-layer “onionlike” micelles comprising DEA cores, DMA inner shells, and PEO coronas. Above pH 7.3, dynamic light scattering studies indicated unimodal, near-monodisperse populations, with mean micelle diameters of 27-84 nm depending on block compositions (for PEO113 triblock copolymers) and polydispersities typically less than 0.10. The average hydrodynamic diameter Dh of the micelles decreased as the solution pH was increased from pH 7.3 to pH 9.0, indicating that the micelles become more compact due to deprotonation of the tertiary amine residues in the DMA and DEA blocks. 1H NMR studies supported a three-layer micelle structure and also revealed changes in the hydrophilicity of the DMA chains in the inner shell during cross-linking, which was achieved by adding the bifunctional alkyl iodide, 1,2-bis(2-iodoethoxy)ethane (BIEE). Selective quaternization of the DMA residues by the BIEE leads to increased hydrophilicity and colloid stability for the shell cross-linked (SCL) micelles. The minimum amount of BIEE required to “lock-in” the micellar structure depended on the thickness of the PEO corona:? shorter PEO chains led to enhanced cross-linking efficiency. At pH 8.5, the hydrodynamic diameter of un-cross-linked micelles increased rapidly above 40-50 °C due to the LCST behavior of the neutral DMA chains in the inner shell. In contrast, the dimensions of the SCL micelles in dilute aqueous solution are independent of temperature. These SCL micelles exhibit reversible swelling on varying the solution pH. At low pH, the DEA cores become protonated and hence hydrophilic. The effect of varying the block composition and the target degree of cross-linking on the structural stability and pH-dependent (de)swelling of the SCL micelles was systematically studied. Longer DEA blocks and lower target degrees of cross-linking led to increased swellability, as expected.