Synthesis of PEGylated poly(amino acid) pentablock copolymers and their self-assembly

Pentablock copolymers with an ABCBA architecture were synthesized by ring-opening polymerization of N-carboxyanhydrides of l-leucine and γ-benzyl l-glutamate using an α, ω-diamino poly(ethylene glycol) (PEG) as macroinitiator. Three different PEGs with molecular weights of 2000, 4600 and 10 000 Da were used and the poly(amino acid) (PAA) block lengths were set to a combined 10 and 40, respectively, repeat units for p(l-Leu) and 40 repeat units for p(l-Glu). The molecular architecture of the resulting pentablock copolymers was determined by the order of monomer addition. The living character of the N-carboxyanhydride ring-opening polymerization enables the formation of multiblock copolymers. The degree of polymerization for the PAA blocks matched the monomer/initiator ratio. A structural switch element, which controls the hydrophilicity of the pentablock copolymers, was incorporated in the form of the p(l-Glu) blocks. The pentablock copolymers became water soluble after hydrolyzing the benzyl ester protective groups. The pentablock copolymers self-assembled into polymeric aggregates ranging in size between 160 and 340 nm. Hydrogels formed readily if the central PEG block had a molecular weight of at least 4600 Da and the terminal A-blocks consisted of p(l-Leu). SEM images confirmed the size ranges of the polymeric aggregates and showed non-distinct spherical aggregates.