Formation of Unimer Nanoparticles by Controlling the Self-Association of Hydrophobically Modified Poly(amino acid)s

Abstract

Amphiphilic block or graft copolymers have been demonstrated to form a variety of self-assembled nano/microstructures in selective solvents. In this study, the self-association behavior of biodegradable graft copolymers composed of poly­(γ-glutamic acid) (γ-PGA) as the hydrophilic segment and l-phenylalanine (Phe) as the hydrophobic segment in aqueous solution was investigated. The association behavior and unimer nanoparticle formation of these γ-PGA-<i>graft</i>-Phe (γ-PGA-Phe) copolymers in aqueous solution were characterized with a focus on the effect of the Phe grafting degree on the intra- and interpolymer association of γ-PGA-Phe. The particle size and number of polymer aggregates (<i>N</i>_agg) in one particle of the γ-PGA-Phe depended on the Phe grafting degree. The size of γ-PGA-Phe with 12, 27, 35, or 42% Phe grafting (γ-PGA-Phe-12, -27, -35, or -42) was about 8–14 nm and the <i>N</i>_agg was about 1, supporting the presence of a unimolecular graft copolymer in PBS. The pyrene fluorescence data indicated that γ-PGA-Phe-35 and -42 have hydrophobic domains formed by the intrapolymer association of Phe attached to γ-PGA. These results suggest that the Phe grafting degree is critical to the association behavior of γ-PGA-Phe and that γ-PGA-Phe-35 and -42 could form unimer nanoparticles. Moreover, when γ-PGA-Phe-42 dissolved in DMSO was added to various concentrations of NaCl solution, the particle size and <i>N</i>_agg could be easily controlled by changing the NaCl concentration during the formation of the particles. These results suggest that biodegradable γ-PGA-Phe is useful for the fabrication of very small nanoparticles. It is expected that γ-PGA-Phe nanoparticles, including unimer particles, will have great potential as multifunctional carriers for pharmaceutical and biomedical applications, such as drug and vaccine delivery systems