Preparation and characterization of PEG-coated silica nanoparticles for oral insulin delivery
Preparation and characterization of PEG-coated silica nanoparticles for oral insulin delivery
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DOI：
10.1016/j.ijpharm.2014.07.049
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发表时间：
2014-10-01
影响因子：
5.8
通讯作者：
Souto, Eliana B.
中科院分区：
文献类型：
--
作者：
Andreani, Tatiana;de Souza, Ana Luiza R.;Souto, Eliana B.
本研究报告了含有口服胰岛素的 PEG 涂层二氧化硅纳米颗粒 (SiNP-PEG) 的生产和表征。制剂中使用高分子量（PEG 20,000）和低分子量（PEG 6000）PEG。 SiNP 采用溶胶凝胶技术生产，随后进行 PEG 吸附，并通过 Franz 扩散池进行体外释放表征。使用外翻的大鼠肠评估体外渗透曲线。 HPLC 方法已被验证可用于测定胰岛素释放和渗透。胰岛素二级结构通过圆二色性（CD）进行。与 SiNP PEG 相比，未包被的 SiNP 可以减缓胰岛素释放。高分子量 PEG 涂层不会显着 (p>0.05) 改变胰岛素释放。缓慢的胰岛素释放归因于胰岛素对二氧化硅表面的硅烷醇基团的亲和力。在 pH 2.0 下，未包衣和 SiNP PEG 的药物释放遵循二级动力学。另一方面，在 pH 6.8 时，SiNP PEG 的最佳拟合为一阶，但 SiNP 表现出玻尔兹曼行为。比较半衰期值，SiNP PEG 20,000 显示出更快的扩散，其次是 Si-PEG 6000 和 SiNP。 CD研究表明，在胃肠道模拟条件下，纳米粒子释放蛋白质后没有发生构象变化。 (C) 2014 Elsevier B.V. 保留所有权利。
The present study reports the production and characterization of PEG-coated silica nanoparticles (SiNP-PEG) containing insulin for oral administration. High (PEG 20,000) and low (PEG 6000) PEG molecular weights were used in the preparations. SiNP were produced by sol gel technology followed by PEG adsorption and characterized for in vitro release by Franz diffusion cells. In vitro permeation profile was assessed using everted rat intestine. HPLC method has been validated for the determination of insulin released and permeated. Insulin secondary structure was performed by circular dichroism (CD). Uncoated SiNP allowed slower insulin release in comparison to SiNP PEG. The coating with high molecular weight PEG did not significantly (p>0.05) alter insulin release. The slow insulin release is attributed to the affinity of insulin for silanol groups at silica surface. Drug release followed second order kinetics for uncoated and SiNP PEG at pH 2.0. On the other hand, at pH 6.8, the best fitting was first-order for SiNP PEG, except for SiNP which showed a Boltzmann behavior. Comparing the values of half-live, SiNP PEG 20,000 showed a faster diffusion followed by Si-PEG 6000 and SiNP. CD studies showed no conformational changes occurring after protein release from the nanoparticles under gastrointestinal simulated conditions. (C) 2014 Elsevier B.V. All rights reserved.