Formation of polyion complex micelles with tunable isoelectric points based on zwitterionic block copolymers

Zwitterionic block copolymers can form polyion complex (PIC) micelles without any additional ionic compounds because their backbones contain both cationic and anionic residues. For the generation of polyion complex (PIC) micelles with tunable isoelectric points (pI), the zwitterionic block copolymers, poly(ethylene oxide)45-b-[poly(2-succinyloxyethyl methacrylate) _x-r-poly(2-(dimethylamino)ethyl methacrylate)_y] (PEO ₄₅-b-(PSEMA_x-r-PDMA_y)) zwitterionic block copolymers were synthesized via atom transfer radical polymerization (ATRP) of 2-hydroxyethyl methacrylate (HEMA) and 2-(dimethylamino)ethyl methacrylate (DMA), and subsequent succinylation of the hydroxy groups on HEMA. The electrostatic interaction between oppositely charged 2-succinyloxyethyl methacrylate (SEMA) and DMA residues led to spontaneous micelle formation of the zwitterionic block copolymers in an aqueous solution. The pH-dependent protonation/deprotonation behavior of the SEMA and DMA residues induced a change in the net charge of the micelle. Since the pIs of PIC micelles are closely related to the SEMA to DMA ratio (x/y) of the zwitterionic block, PIC micelles with certain pI values, which can be predicted by simple calculations based on the average pKa values of DMA and SEMA, can be easily tailored to achieve our objectives.