pH-induced micelle formation of poly(histidine-co-phenylalanine)-block-poly(ethylene glycol) in aqueous media.

Poly[(L-histidine)-co-(L-phenylalanine)]-block-poly(ethylene glycol) (HF-b-PEG) diblock copolymers were synthesized to be used for preparation of pH-sensitive polymeric micelles. First, HF block was synthesized by ring opening copolymerization of L-histidine and L-phenylalanine N-carboxyanhydride, and then the resulting copolymer was coupled with PEG. The pKa value of diblock copolymer can be controlled by adjusting the histidine/phenylalanine ratio in HF block. It is observed that the block copolymers form micelles in aqueous media and that the micelles are spherical in shape with a unimodal distribution. The micelle is formed at pH higher than pKa of block copolymer while it is not formed at lower pH. This is because the protonation of histidine residue in the HF block converts the hydrophobic core into hydrophilic one at lower pH. Acid-Base titration profile of HF41(5600)-b-PEG, HF56(5500)-b-PEG, H(5100)-b-PEG and 0.1 N NaCl.