The angiogenic effect of ONO-1301, a novel long-acting prostacyclin agonist loaded in PLGA microspheres prepared using different molecular weights of PLGA, in a murine sponge model
The angiogenic effect of ONO-1301, a novel long-acting prostacyclin agonist loaded in PLGA microspheres prepared using different molecular weights of PLGA, in a murine sponge model
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DOI：
10.3109/03639045.2013.828220
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发表时间：
2014-11-01
影响因子：
3.4
通讯作者：
Uchida, Takahiro
中科院分区：
文献类型：
--
作者：
Hazekawa, Mai;Morihata, Kana;Uchida, Takahiro
本研究的目的是评价局部应用三种类型的ONO-1301负载聚（丙交酯-共-乙交酯）微球（ONO-1301 PLGA MS）的血管生成作用。采用溶剂挥发法，以PLGA 5010、5020和5050（分子量分别为10 K、20 K和50 K）制备ONO-1301 PLGA MS。丙交酯：乙交酯的比例固定为50：50;仅分子量变化。微球的平均直径几乎为25 mm，并且装载效率至少为70%。在体外药物释放试验中以及通过对大鼠给予三种类型的ONO-1301 PLGA MS 28天后测量皮下血浆水平，证实了缓释效果及其对所用聚合物分子量的依赖性。在鼠海绵模型中，将三种类型的ONO-1301 PLGA MS在皮下放置的海绵中给予小鼠，并以预定间隔测量海绵中的血红蛋白和肝细胞生长因子（HGF）水平，最长28天。获得的血红蛋白和HGF水平显著高于每日施用ONO-1301粉末后获得的血红蛋白和HGF水平。另外的体内荧光成像显示PLGA MS在海绵中保留28天。总之，用PLGA三种不同分子量制备的三种类型的ONO-1301 PLGA MS在小鼠海绵模型中局部应用时抑制突释，刺激血管生成。因此，该制剂可能能够改善某些类型血管疾病的临床表现。
The purpose of this study was to evaluate the angiogenic effect of topical application of three types of ONO-1301-loaded poly (lactide-co-glycolide) microspheres (ONO-1301 PLGA MS). ONO-1301 PLGA MS were prepared with PLGA 5010, 5020 and 5050 (with molecular weights of 10 K, 20 K and 50 K, respectively), using the solvent evaporation method. The lactide: glycolide ratio was fixed at 50: 50; only the molecular weight was varied. The microspheres had an average diameter of almost 25 mm, and a loading efficiency of at least 70%. The sustained-release effect and its dependence on the molecular weight of the polymer used was confirmed in an in vitro drug-release test and by measuring subcutaneous plasma levels after administration of the three types of ONO-1301 PLGA MS to rats for 28 days. In the murine sponge model, the three types of ONO-1301 PLGA MS were administered to mice in a subcutaneously placed sponge and hemoglobin and hepatocyte growth factor (HGF) levels in the sponge were measured at predefined intervals up to 28 days. The hemoglobin and HGF levels obtained were significantly higher than those obtained after daily administration of ONO-1301 powder. Additional in vivo fluorescence imaging showed that PLGA MS remained in the sponge for 28 days. In conclusion, the three types of ONO-1301 PLGA MS prepared with PLGA three different molecular weight suppress the burst release, stimulate angiogenesis on topical application in a murine sponge model. This formulation may therefore be capable of improving the clinical picture in some types of vascular disease.