Preparation and characterization of biodegradable nanoparticles based on poly(gamma-glutamic acid) with l-phenylalanine as a protein carrier.
The objective of the present study was to prepare nanoparticles composed of poly(gamma-glutamic acid) (gamma-PGA) and l-phenylalanine ethylester (l-PAE) in order to evaluate the possibility of using these nanoparticles as protein carriers. Novel amphiphilic graft copolymers composed of gamma-PGA as the hydrophilic backbone and l-PAE as the hydrophobic segment were successfully synthesized by grafting l-PAE to gamma-PGA using water-soluble carbodiimide (WSC). Due to their amphiphilic properties, the gamma-PGA-graft-l-PAE copolymers were able to form nanoparticles. The size of the gamma-PGA nanoparticles was measured by photon correlation spectroscopy (PCS) and showed a monodispersed size distribution with a mean diameter ranging from 150 to 200 nm. The solvents selected to prepare the gamma-PGA nanoparticles by a precipitation and dialysis method affected the particle size distribution. To evaluate the feasibility of vehicles for these proteins, we prepared protein-loaded gamma-PGA nanoparticles by surface immobilization and encapsulation methods. Ovalbumin (OVA) was used as a model protein and was immobilized onto the gamma-PGA nanoparticles or encapsulated into the inner core of these nanoparticles. Moreover, these OVA-encapsulated gamma-PGA nanoparticles could be preserved by freeze-drying process. The results of cytotoxicity tests showed that the gamma-PGA and gamma-PGA nanoparticles did not cause any relevant cell damage. It is expected that biodegradable gamma-PGA nanoparticles can immobilize proteins, peptides, plasmid DNA and drugs onto their surfaces and/or into the nanoparticles. These nanoparticles are potentially useful in pharmaceutical and biomedical applications.
Akagi
Takami
T
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita 565-0871, Japan.
Kaneko
Tatsuo
T
Kida
Toshiyuki
T
Akashi
Mitsuru
M
D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004151:Dipeptides / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004563:Electrochemistry; D005612:Freeze Drying; D018922:HL-60 Cells; D006801:Humans; D008422:Materials Testing; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures; D010047:Ovalbumin / Q000737:chemistry; D010316:Particle Size; D010649:Phenylalanine / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000737:chemistry
D004151:Dipeptides; D004337:Drug Carriers; C063009:phenylalanylphenylalanine methyl ester; D011099:Polyglutamic Acid; D010649:Phenylalanine; D010047:Ovalbumin