IN-VITRO DRUG-RELEASE BEHAVIOR OF D,L-LACTIDE/GLYCOLIDE COPOLYMER (PLGA) NANOSPHERES WITH NAFARELIN ACETATE PREPARED BY A NOVEL SPONTANEOUS EMULSIFICATION SOLVENT DIFFUSION METHOD

被引:107
作者
NIWA, T [1 ]
TAKEUCHI, H [1 ]
HINO, T [1 ]
KUNOU, N [1 ]
KAWASHIMA, Y [1 ]
机构
[1] GIFU PHARMACEUT UNIV,DEPT PHARMACEUT ENGN,GIFU 502,JAPAN
关键词
D O I
10.1002/jps.2600830527
中图分类号
R914 [药物化学];
学科分类号
100701 ;
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 ef fact of th 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 that 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. In the test solution no. 2 (pH = 6.8), the drug release rate from the nanospheres was much slower than that in solution no. 1.
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页码:727 / 732
页数:6
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