艾塞那肽载入介孔二氧化硅纳米粒的缓释研究：体外表征与体内评价
Sustained-release study on Exenatide loaded into mesoporous silica nanoparticles: in vitro characterization and in vivo evaluation.
作者信息
Chen Cuiwei, Zheng Hongyue, Xu Junjun, Shi Xiaowei, Li Fanzhu, Wang Xuanshen
机构信息
Department of Pharmaceutics, Zhejiang Chinese Medical University, Hangzhou, 311042, China.
Libraries of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
出版信息
Daru. 2017 Sep 4;25(1):20. doi: 10.1186/s40199-017-0186-9.
BACKGROUND
Exenatide (EXT), the first glucagon-like peptide-1 receptor agonist, has been approved as an adjunctive therapy for patients with type 2 diabetes. Due to EXT's short half-life, EXT must be administrated by continuous subcutaneous (s.c.) injection twice daily. In previous studies, many studies on EXT loaded into polymer materials carriers for sustained release had been reported. However, these carriers have some defects, such as hydrophobicity, low surface energy, low mechanical strength, and poor chemical stability. Therefore, this study aims to develop a novel drug delivery system, which is EXT loaded into well-ordered hexagonal mesoporous silica structures (EXT-SBA-15), to control the sustainability of EXT.
METHODS
SBA-15 was prepared by hydrothermal method with uniform size. Morphology of SBA-15 was employed by transmission electron microscopy. The pore size of SBA-15 was characterized by N adsorption-desorption isotherms. The in vitro drug release behavior and pharmacokinetics of EXT-SBA-15 were investigated. Furthermore, the blood glucose levels of diabetic mice were monitored after subcutaneous injection of EXT-Sol and EXT-SBA-15 to evaluate further the stable hypoglycemic effect of EXT-SBA-15.
RESULTS
EXT-SBA-15 showed a higher drug loading efficiency (15.2 ± 2.0%) and sustained-release features in vitro. In addition, pharmacokinetic studies revealed that the EXT-SBA-15 treatment group extended the half-life t to 14.53 ± 0.70 h compared with that of the EXT solution (EXT-Sol) treatment group (0.60 ± 0.08 h) in vivo. Results of the pharmacodynamics study show that the EXT-SBA-15 treatment group had inhibited blood glucose levels below 20 mmol/L for 25 days, and the lowest blood glucose level was 13 mmol/L on the 10th day.
CONCLUSIONS
This study demonstrates that the EXT-SBA-15 delivery system can control the sustainability of EXT and contribute to improve EXT clinical use.
背景
艾塞那肽（EXT）是首个获批的胰高血糖素样肽-1受体激动剂，已被批准作为2型糖尿病患者的辅助治疗药物。由于EXT半衰期短，必须每天两次通过皮下连续注射给药。在先前的研究中，已有许多关于将EXT负载到聚合物材料载体中以实现缓释的研究报道。然而，这些载体存在一些缺陷，如疏水性、低表面能、低机械强度和化学稳定性差。因此，本研究旨在开发一种新型药物递送系统，即将EXT负载到有序的六方介孔二氧化硅结构（EXT-SBA-15）中，以控制EXT的缓释性能。
方法
采用水热法制备尺寸均匀的SBA-15。通过透射电子显微镜观察SBA-15的形态。用N2吸附-脱附等温线表征SBA-15的孔径。研究EXT-SBA-15的体外药物释放行为和药代动力学。此外，皮下注射EXT溶液（EXT-Sol）和EXT-SBA-15后监测糖尿病小鼠的血糖水平，以进一步评估EXT-SBA-15的稳定降血糖效果。
结果
EXT-SBA-15在体外表现出较高的载药效率（15.2±2.0%）和缓释特性。此外，药代动力学研究表明，与EXT溶液（EXT-Sol）治疗组相比，EXT-SBA-治疗组在体内将半衰期延长至14.53±0.70小时（EXT-Sol治疗组为0.60±0.08小时）。药效学研究结果表明，EXT-SBA-15治疗组在25天内将血糖水平抑制在20 mmol/L以下，第10天最低血糖水平为13 mmol/L。
结论
本研究表明，EXT-SBA-15递送系统可以控制EXT的缓释性能，有助于改善EXT的临床应用。
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