Preparation and characterization of low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as FGF-2 carrier.
Preparation and characterization of low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as FGF-2 carrier.
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DOI：
10.2147/ijn.s8692
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发表时间：
2010-04-07
影响因子：
8
通讯作者：
Ishihara M
中科院分区：
文献类型：
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作者：
Mori Y;Nakamura S;Kishimoto S;Kawakami M;Suzuki S;Matsui T;Ishihara M
我们生产了低分子量肝素/鱼精蛋白纳米颗粒（LMW-H/P NPs）作为肝素结合生长因子（如成纤维细胞生长因子-2（FGF-2））的载体。低分子量肝素（MW：约5000 Da，6.4 mg/mL）和鱼精蛋白（MW：约3000 Da，10 mg/mL）以7：3（体积：体积）的比例混合，得到微粒（直径1-6 μm）的分散体。在本研究中，将稀释的低分子量肝素盐水溶液（0.32 mg/mL）与稀释的鱼精蛋白（0.5 mg/mL）以7：3（体积：体积）的比例混合，得到可溶性纳米颗粒（直径为112.5 ± 46.1 nm）。然后可以通过添加2 mg/mL葡聚糖（MW：178-217 kDa）来稳定所产生的NP，并且在冻干透析的LMW-H/NP溶液后保持可溶。然后，我们评估了LMW-H/P NP保护FGF-2活性的能力。FGF-2和LMW-H/P NP之间的相互作用显著延长了FGF-2的生物半衰期。此外，FGF-2分子在LMW-H/P NP存在下被保护免于通过加热和蛋白水解失活。
We produced low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as a carrier for heparin-binding growth factors, such as fibroblast growth factor-2 (FGF-2). A mixture of low-molecular-weight heparin (MW: about 5000 Da, 6.4 mg/mL) and protamine (MW: about 3000 Da, 10 mg/mL) at a ratio of 7:3 (vol:vol) yields a dispersion of microparticles (1–6 μm in diameter). In this study, diluted low-molecular-weight heparin solution in saline (0.32 mg/mL) mixed with diluted protamine (0.5 mg/mL) at a ratio at 7:3 (vol:vol) resulted in soluble nanoparticles (112.5 ± 46.1 nm in diameter). The generated NPs could be then stabilized by adding 2 mg/mL dextran (MW: 178–217 kDa) and remained soluble after lyophilization of dialyzed LMW-H/P NP solution. We then evaluated the capacity of LMW-H/P NPs to protect activity of FGF-2. Interaction between FGF-2 and LMW-H/P NPs substantially prolonged the biological half-life of FGF-2. Furthermore, FGF-2 molecules were protected from inactivation by heat and proteolysis in the presence of LMW-H/P NPs.