PLGA公司
化学
溶剂
水溶液
毒品携带者
聚乙烯醇
丙酮
共聚物
核化学
色谱法
化学工程
高分子化学
有机化学
聚合物
药物输送
体外
生物化学
工程类
作者
Toshiyuki Niwa,Hirofumi Takeuchi,Tomoaki Hino,Noriyuki Kunou,Yasunaru Kawashima
标识
DOI:10.1002/jps.2600830527
摘要
Nanospheres with D,L-lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion method. Nafarelin acetate (NA), a luteinizing hormone-releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone-dichloromethane-water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200-300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of the rapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water-soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug-release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found tht the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the porous matrix structure.(ABSTRACT TRUNCATED AT 250 WORDS)
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