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-graft-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 (N(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 N(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 N(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.

Advances in Click Chemistry for Single-Chain Nanoparticle Construction

“…Reactive functional groups NC/DC bonding interactions Benzamide [26] Benzamide hydrogen bonding * 2-Ureido-Pyrimidone (UPy) [43] UPy dimerization * Coumarin [35] Coumarin photo-dimerization ** Benzaldehyde [32] Acylhydrazone formation ** -Ketoester [27] Enamine formation ** Methyl viologen + Naphtyl [37] Cucurbit[n]uril complexation * L-Phenylalanine (Phe) [55] Hydrophobic Phe-Phe interactions * Aminophenyl disulfide [44] Disulfide formation ** * NC bonding interactions. ** DC bonding interactions.…”

One-Step Electrodeposition of Self-Assembled Colloidal Particles: A Novel Strategy for Biomedical Coating

“…9,10 As reported in previous works, amphiphilic γ-PGA derivatives can self-assemble into micellar aggregates with various morphologies, such as spheres, rods, and vesicles. 11,12 The attractive advantages of these nanoparticles include a high specific surface area, green nature, nontoxicity, biodegradability, and flexibility in internal or surface functionalities. Although γ-PGA-based particles have potential applications as drug delivery, protein, gene, and vaccine carriers because of these outstanding properties, 13−16 research that expands the application of γ-PGA-based particles in biomedical coating systems is lacking.…”

Self-assembly and emulsification of dopamine-modified hyaluronan

“…HA-DOPA nanoparticles were prepared by a direct dispersion method according to a previous report (Akagi, Piyapakorn, & Akashi, 2012). HA-DOPA were directly dissolved or dispersed in deionized water with stirring overnight and then sonicated (AS ONE corporation, VS-150) at 150 W for 2 min.…”

“…The critical aggregation concentrations (CAC) of HA-DOPA were determined as described elsewhere (Akagi et al, 2012). Briefly, 10 L of pyrene in acetone solution at a concentration of 1 × 10 −4 M was added into a series of glass vessels.…”