Synthesis and structure formation of block copolymers of poly(ethylene glycol) with homopolymers and copolymers of L-glutamic acid γ-benzyl ester and L-leucine in water

Block copolymers consisting of blocks of poly(amino acid)s (PAAs) derived from naturally occurring l-amino acids and biocompatibilizing poly(ethylene glycol) (PEG) are of interest for biomedical applications because of their compatibility, partial degradability, and, depending on their molecular architecture, unique self-assembly behavior. PEGylated PAAs were synthesized by alpha-methoxy-omega-amino PEG-initiated ring-opening polymerization, ROP, of the N-carboxyanhydrides, NCAs, of l-glutamic acid gamma-benzyl ester. The molecular weights of the resulting di- and triblock copolymers were well controlled with narrow polydispersities, and the block copolymers were obtained in high yields (> 90 %). PEGylated PAA diblock copolymers with a copolymer block of PAAs were obtained when the amino acid NCAs were polymerized as a mixture and triblock copolymers with two PAA hompolymer blocks resulted from the successive addition of the respective NCAs. Dynamic light scattering indicated that these block copolymers self-assemble when exposed to a selective solvent into micelles with hydrodynamic radii between 7 and 10 nm, which aggregate into larger structures with radii ranging between 27 and 40 nm. The coexistence and sizes of the two types of particles were corroborated by small-angle neutron scattering analyses. A detailed analysis of the micelle core structures by transmission electron microscopy suggests that the cores of the micelles do not form perfect spheres and thereby enable their continued aggregation, which is further aided by the immiscibility and subsequent phase separation of poly(l-leucine) blocks that constitute the PAA block.