Poly(ε-Caprolactone)/Eudragit Nanoparticles for Oral Delivery of Aspart-Insulin in the Treatment of Diabetes
Poly(ε-Caprolactone)/Eudragit Nanoparticles for Oral Delivery of Aspart-Insulin in the Treatment of Diabetes
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DOI：
10.1002/jps.21874
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发表时间：
2010-02-01
影响因子：
3.8
通讯作者：
Maincent, Philippe
中科院分区：
文献类型：
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作者：
Damge, Christiane;Socha, Marie;Maincent, Philippe
用可生物降解的聚酯（聚（ε-己内酯））和聚阳离子不可生物降解的丙烯酸聚合物（Eudragit（R）RS）的共混物制备的纳米颗粒已被用作口服施用短效胰岛素类似物β-胰岛素的药物载体。直径约700 nm的胰岛素负载纳米粒包封97.5%的胰岛素，并且能够在中性介质中体外释放约70%的其含量超过24小时。当口服给药于糖尿病大鼠时，负载胰岛素的纳米颗粒（50 IU/kg）在较长时间内降低空腹血糖，并以时间依赖性方式改善对葡萄糖的血糖反应，在给药后12至24小时之间效果最大。同时，血浆胰岛素水平升高。然而，较高（100 IU/kg）和较低（25 IU/kg）剂量的胰岛素未产生任何生物学效应。结论是，由聚（ε-己内酯）/Eudragit（R）RS组成的聚合物纳米颗粒能够保持胰岛素类似物β-胰岛素的生物活性;然而，与仅工作6-8小时的常规胰岛素相比，餐后峰抑制延长超过24小时。这种效应可能是由于β-胰岛素的单体构型，它可能比常规胰岛素更好地被肠粘膜吸收。(C)2009 Wiley-Liss，Inc.和American Pharmacologist Association J Pharm Sci 99：879-889，2010
Nanoparticles prepared with a blend of a biodegradable polyester (poly(epsilon-caprolactone)) and a polycationic nonbiodegradable acrylic polymer (Eudragit (R) RS) have been used as a drug carrier for oral administration of a short-acting insulin analogue, aspart-insulin. Insulin-loaded nanoparticles, about 700 nm in diameter, encapsulated 97.5% of insulin and were able to release about 70% of their content in vitro in a neutral medium over 24h. When administered orally to diabetic rats, insulin-loaded nanoparticles (50 IU/kg) decreased fasted glycemia for a prolonged period of time and improved the glycemic response to glucose in a time-dependent manner, with a maximal effect between 12 and 24h after their administration. In parallel, plasma insulin levels increased. However, higher (100 IU/kg) and lower (25 IU/kg) doses of insulin did not exert any biological effect. It is concluded that polymeric nanoparticles composed of poly(epsilon-caprolactone)/Eudragit (R) RS are able to preserve the biological activity of the insulin analogue aspart-insulin; however, the postprandial peak suppression was prolonged more than 24h by comparison with regular insulin working only 6-8 h. This effect may be explained by the monomeric configuration of aspart-insulin, which is probably better taken up by the intestinal mucosa than regular insulin. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:879-889, 2010