Fragmin/protamine microparticles to adsorb and protect HGF and to function as local HGF carriers in vivo
Fragmin/protamine microparticles to adsorb and protect HGF and to function as local HGF carriers in vivo
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DOI：
10.1016/j.actbio.2012.08.003
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发表时间：
2013-01-01
影响因子：
9.7
通讯作者：
Kanatani, Yasuhiro
中科院分区：
文献类型：
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作者：
Kishimoto, Satoko;Ishihara, Masayuki;Kanatani, Yasuhiro
肝细胞生长因子（HGF）在组织修复中的临床疗效可以通过高亲和力、生物相容性的药物载体来大大增强，这些药物载体可以维持HGF在靶点的生物活性并调节其释放。制备了0.5 ~ 3.0 μ m的低分子量肝素/鱼精蛋白微粒（F/P MPs）作为HGF控释载体。F/P MPs每mg MPs固定超过3 μ g的HGF，并逐渐将吸收的HGF释放到培养基中，半释放时间约为5天。与单独使用HGF相比，含HGF的F/P MPs通过延长生物半衰期，显著增强了HGF对培养的人微血管内皮细胞的有丝分裂作用，其与F/P MPs的结合可保护HGF免受高温和蛋白水解失活。F/P MPs在小鼠皮下注射后8天消失，表明它们被快速生物降解。此外，注射含HGF的F/P MPs后8天，大（直径>= 200 μ m或含>= 100个红细胞）和中（直径20-200 μ m或含10-100个红细胞）管腔毛细血管的数量明显高于单独注射HGF或F/P MPs后8天。再者，小（径）数
The clinical efficacy of hepatocyte growth factor (HGF) in tissue repair can be greatly enhanced by high affinity, biocompatible drug carriers that maintain the bioactivity and regulate release at the target site. We produced 0.5-3.0 mu m fragmin (low molecular weight heparin)/protamine microparticles (F/P MPs) as carriers for the controlled release of HGF. F/P MPs immobilized more than 3 mu g of HGF per mg of MPs and gradually released the absorbed HGF into the medium with a half-release time of approximately 5 days. Compared with HGF alone, HGF-containing F/P MPs substantially enhanced the mitogenic effect of HGF on cultured human microvascular endothelial cells, by prolonging the biological half-life, and its conjugation to F/P MPs protected HGF from heat and proteolytic inactivation. F/P MPs disappeared 8 days after subcutaneous injection in mice, suggesting that they are rapidly biodegraded. Furthermore, the number of large (diameter >= 200 mu m or containing >= 100 erythrocytes) and medium (diameter 20-200 mu m or containing 10-100 erythrocytes) lumen capillaries 8 days after injection of HGF-containing F/P MPs was significantly higher than that after injection of HGF or F/P MPs alone. Furthermore, the number of small (diameter