Murakami H, Kobayashi M, Takeuchi H, Kawashima Y
Pharmaceutics Research Laboratory, Tanabe Seiyaku Co., Ltd. 16-89 Kashima 3-chome, Yodogawa-ku, Osaka, Japan.
Int J Pharm. 1999 Oct 5;187(2):143-52. doi: 10.1016/s0378-5173(99)00187-8.
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.
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.
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.
The proposed modified-SESD method can be used to provide PLGA nanoparticles of satisfactory quality at an acceptable yield for industrial purposes.
本研究的目的是通过改进自发乳化溶剂扩散(SESD)法建立一种聚(DL-丙交酯-乙交酯)(PLGA)纳米粒的新制备方法,并基于PLGA和聚乙烯醇(PVA)在制备体系中的相分离原理阐明纳米粒的形成机制。
采用改进的SESD法,使用由两种与水混溶的有机溶剂组成的各种溶剂体系制备PLGA纳米粒,其中一种溶剂对PLGA的亲和力比对PVA的亲和力大,另一种溶剂对PVA的亲和力比对PLGA的亲和力大。评估了PLGA纳米粒的产率、粒径、粒径分布和PVA含量,并阐明了聚合物的相分离行为。
改进的SESD法在有机溶剂二元混合物的广泛组成比范围内提供了良好的PLGA纳米粒产率。考察了几个工艺参数,包括PLGA的进料量、PLGA浓度和PVA浓度,以获得最佳制备条件。通过冷冻干燥获得PLGA纳米粒的离散粉末。即使经过几次超滤洗涤处理,PLGA纳米粒的PVA含量也没有变化,表明表面吸附很强。发现二元溶剂混合物以及有机相和水相中聚合物浓度的适当选择可以提供优异的产率和良好的PLGA纳米粒物理性质。
所提出的改进SESD法可用于以可接受的产率提供质量令人满意的PLGA纳米粒,用于工业目的。