Preparation of poly(DL-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method.
OBJECTIVE
The objectives of this study were to establish a new preparation method for poly(DL-lactide-co-glycolide) (PLGA) nanoparticles by modifying the spontaneous emulsification solvent diffusion (SESD) method and to elucidate the mechanism of nanoparticle formation on the basis of the phase separation principle of PLGA and poly(vinyl alcohol) (PVA) in the preparation system.


METHODS
PLGA nanoparticles were prepared by the modified-SESD method using various solvent systems consisting of two water-miscible organic solvents, in which one solvent has more affinity to PLGA than to PVA and the other has more affinity to PVA than to PLGA. The yield, particle size, size distribution and PVA content of the PLGA nanoparticles were evaluated, and the phase separation behaviors of the polymers were elucidated.


RESULTS
The modified-SESD method provided a good yield of PLGA nanoparticles over a wide range of composition ratios in the binary mixture of organic solvents. Several process parameters, including the fed amount of PLGA, PLGA concentration and PVA concentration were examined to achieve the optimum preparation conditions. The discrete powder of PLGA nanoparticles was obtained by freeze-drying. No change in the PVA content of PLGA nanoparticles was observed even after several times of washing treatment by ultrafiltration, suggesting a strong surface adsorption. It was found that the appropriate selections of binary solvent mixtures and polymeric concentrations in both organic and aqueous phases could provide excellent yield and favorable physical properties of PLGA nanoparticles.


CONCLUSIONS
The proposed modified-SESD method can be used to provide PLGA nanoparticles of satisfactory quality at an acceptable yield for industrial purposes.
Murakami
H
H
Pharmaceutics Research Laboratory, Tanabe Seiyaku Co., Ltd. 16-89 Kashima 3-chome, Yodogawa-ku, Osaka, Japan.
Kobayashi
M
M
Takeuchi
H
H
Kawashima
Y
Y
D004058:Diffusion; D016503:Drug Delivery Systems; D004655:Emulsions; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011142:Polyvinyl Alcohol; D012997:Solvents
D004655:Emulsions; D011108:Polymers; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011142:Polyvinyl Alcohol