Biodegradable Nano-aggregates of Star-Shaped 8-arm PEG-PLLA Block Co-polymers for Encapsulation of Water-Soluble Macromolecules.
A series of amphiphilic 8-arm PEG-b-PLLA co-polymers with star-shaped structure was synthesized through ring-opening polymerization of L-lactide (L-LA) in the presence of 8-arm PEG as a macroinitiator by varying feeding molar rations of L-LA to 8-arm PEG. 8-arm PEG-b-PLLA co-polymers having certain PEG content and PEG length were found to self-assemble into nano-aggregates in aqueous solutions. The size and the morphology of the nano-aggregates were investigated by dynamic light scattering and (1)H-NMR in CDCl3 and D2O. The results indicate that the average diameter was ca. 150 nm, the surface of the nano-aggregates was covered by PEG chains and the PLLA cores formed by hydrophobic interaction are located inside of the nano-aggregates. FITC-dextran molecules, as model for water-soluble macromolecular drugs, were successfully encapsulated into 8-arm PEG-b-PLLA nano-aggregates by simple addition of FITC-dextran to the aqueous phase during the self-assembly process. This result suggests that the nanoaggregates have a vesicle-like morphology. The nano-aggregates dissociated gradually in the order of weeks in PBS (pH 7.4, ionic strength 140 mM) at 37°C. Thus, the novel nano-aggregates of 8-arm PEG-b-PLLA can be expected to have advantages, such as long circulation times, as drug carriers which show sustained release of loaded macromolecular drugs such as antibodies and DNA vaccines in the blood stream.
Nagahama
K
K
a Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering and High Technology Research Center, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan.
Saito
T
T
Ouchi
T
T
Ohya
Y
Y
D002725:Chloroform / Q000737:chemistry; D017666:Deuterium Oxide / Q000737:chemistry; D003911:Dextrans / Q000008:administration & dosage; D004146:Dioxanes / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry*; D000067493:Dynamic Light Scattering; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives; D005452:Fluoresceins / Q000008:administration & dosage; D007773:Lactates / Q000138:chemical synthesis* / Q000737:chemistry*; D008422:Materials Testing; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry*; D058105:Polymerization; D066244:Proton Magnetic Resonance Spectroscopy; D012996:Solutions; D014867:Water / Q000737:chemistry
D003911:Dextrans; D004146:Dioxanes; D004337:Drug Carriers; D005452:Fluoresceins; D007773:Lactates; D012996:Solutions; C015219:fluorescein isothiocyanate dextran; C088513:poly(lactic acid-ethylene glycol); D014867:Water; D011092:Polyethylene Glycols; D002725:Chloroform; C091880:dilactide; D016650:Fluorescein-5-isothiocyanate; D017666:Deuterium Oxide; C007740:fluorexon