Hydrolytic and Enzymatic Degradation of Nanoparticles Based on Amphiphilic Poly(γ-glutamic acid)-graft-l-Phenylalanine Copolymers

Amphiphilic graft copolymers consisting of poly(γ-glutamic acid) (γ-PGA) as the hydrophilic backbone and l-phenylalanine ethylester (L-PAE) as the hydrophobic side chain were synthesized by grafting L-PAE to γ-PGA. The nanoparticles were prepared by a precipitation method, and about 200 nm-sized nanoparticles were obtained due to their amphiphilic properties. The hydrolytic and enzymatic degradation of these γ-PGA nanoparticles was studied by gel permeation chromatography (GPC), scanning electron microscopy (SEM), dynamic light scattering (DLS) and 1H NMR measurements. The hydrolysis ratio of γ-PGA and these hydrophobic derivatives was found to decrease upon increasing the hydrophobicity of the γ-PGA derivates. The pH had an effect on the hydrolytic degradation of the polymer. The hydrolysis of the polymer could be accelerated by alkaline conditions. The degradation of the γ-PGA backbone by γ-glutamyl transpeptidase (γ-GTP) resulted in a dramatic change in nanoparticle morphology. With increasing time, the γ-PGA nanoparticles began to decrease in size and finally disappeared completely. Moreover, the γ-PGA nanoparticles were degraded by four different enzymes (Pronase E, protease, cathepsin B and lipase) with different degradation patterns. The enzymatic degradation of the nanoparticles occurred via the hydrolysis of γ-PGA as the main chain and L-PAE as the side chain. In the case of the enzymatic degradation of γ-PGA nanoparticles with Pronase E, the size of the nanoparticles increased during the initial degradation stage and decreased gradually when the degradation time was extended. Nanoparticles composed of biodegradable amphiphilic γ-PGA with reactive function groups can undergo further modification and are expected to have a variety of potential pharmaceutical and biomedical applications, such as drug and vaccine carriers.