Preparation of Water-Soluble Polyion Complex (PIC) Micelles Covered with Amphoteric Random Copolymer Shells with Pendant Sulfonate and Quaternary Amino Groups

An amphoteric random copolymer (P(SA)(91)) composed of anionic sodium 2-acrylamido-2-methylpropanesulfonate (AMPS, S) and cationic 3-acrylamidopropyl trimethylammonium chloride (APTAC, A) was prepared via reversible addition-fragmentation chain transfer (RAFT) radical polymerization. The subscripts in the abbreviations indicate the degree of polymerization (DP). Furthermore, AMPS and APTAC were polymerized using a P(SA)(91) macro-chain transfer agent to prepare an anionic diblock copolymer (P(SA)(91)S(67)) and a cationic diblock copolymer (P(SA)(91)A(88)), respectively. The DP was estimated from quantitative (13)C NMR measurements. A stoichiometrically charge neutralized mixture of the aqueous P(SA)(91)S(67) and P(SA)(91)A(88) formed water-soluble polyion complex (PIC) micelles comprising PIC cores and amphoteric random copolymer shells. The PIC micelles were in a dynamic equilibrium state between PIC micelles and charge neutralized small aggregates composed of a P(SA)(91)S(67)/P(SA)(91)A(88) pair. Interactions between PIC micelles and fetal bovine serum (FBS) in phosphate buffered saline (PBS) were evaluated by changing the hydrodynamic radius (R(h)) and light scattering intensity (LSI). Increases in R(h) and LSI were not observed for the mixture of PIC micelles and FBS in PBS for one day. This observation suggests that there is no interaction between PIC micelles and proteins, because the PIC micelle surfaces were covered with amphoteric random copolymer shells. However, with increasing time, the diblock copolymer chains that were dissociated from PIC micelles interacted with proteins.