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聚(羟乙基甲基丙烯酸酯)纳米凝胶的开发用于有效的口服胰岛素传递。

Development of poly(hydroxyethyl methacrylate) nanogel for effective oral insulin delivery.

机构信息

a Department of Geriatrics , Southwest Hospital Affiliated to the Third Military Medical University , Chongqing , China.

出版信息

Pharm Dev Technol. 2018 Apr;23(4):351-357. doi: 10.1080/10837450.2017.1295064. Epub 2017 Mar 3.

Abstract

Because of uncomfortable, painful and even deleterious effects of daily injection of insulin, extensive efforts are being made worldwide for developing noninvasive drug delivery systems, especially via the oral route. In this study, we synthesized hydroxyethyl methacrylate (HEMA) nanogel via emulsion polymerization method. The morphology and stability of the nanogel were characterized by scanning electronic microscope and dynamic light scattering. In vivo results showed the soft HEMA nanogel had longer half-live in the body circulation and exhibited almost negligible uptake by the macrophage cells as compared with blank cells. For the FITC-dextran tracking for intestinal penetration, the results indicated that the FITC-dextran in the soft nanogel penetrated faster from the inner side of the abdominal segment, which explained why the soft HEMA nanogel could promote intestinal absorption of encapsulated insulin. In vivo delivery of insulin encapsulated in the soft HEMA nanogel sustained blood glucose control for 12 h, and the overall bioavailability of administrated insulin was much higher than free insulin. Our results showed that the insulin-loaded HEMA nanogel was able to efficiently control blood glucose as a delivery system, suggesting the HEMA nanogel using emulsion polymerization could be an alternative carrier for oral insulin delivery.

摘要

由于每日注射胰岛素会带来不适、疼痛甚至有害的影响,全球范围内正在进行广泛的努力,以开发非侵入性的药物输送系统,特别是通过口服途径。在本研究中,我们通过乳液聚合方法合成了羟乙基甲基丙烯酸酯(HEMA)纳米凝胶。通过扫描电子显微镜和动态光散射对纳米凝胶的形态和稳定性进行了表征。体内实验结果表明,与空白细胞相比,柔软的 HEMA 纳米凝胶在体内循环中的半衰期更长,几乎可以忽略不计地被巨噬细胞摄取。对于 FITC-葡聚糖的肠道穿透跟踪,结果表明,FITC-葡聚糖在柔软纳米凝胶中的穿透速度更快,从腹部段的内侧开始,这解释了为什么柔软的 HEMA 纳米凝胶可以促进包封胰岛素的肠道吸收。包封在柔软的 HEMA 纳米凝胶中的胰岛素的体内递送能持续控制血糖 12 小时,并且给予的胰岛素的整体生物利用度远高于游离胰岛素。我们的结果表明,载有胰岛素的 HEMA 纳米凝胶作为递送系统能够有效地控制血糖,这表明使用乳液聚合的 HEMA 纳米凝胶可以作为口服胰岛素递送的替代载体。

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