Eudragit S100-Coated Chitosan Nanoparticles Co-loading Tat for Enhanced Oral Colon Absorption of Insulin
Eudragit S100-Coated Chitosan Nanoparticles Co-loading Tat for Enhanced Oral Colon Absorption of Insulin
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Eudragit S100 涂层壳聚糖纳米颗粒共同负载 Tat，增强口腔结肠对胰岛素的吸收
DOI：
10.1208/s12249-016-0594-z
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发表时间：
2017-05-01
影响因子：
3.3
通讯作者：
Deng, Zeyuan
中科院分区：
文献类型：
--
作者：
Chen, Shuangxi;Guo, Feng;Deng, Zeyuan
为了改善胰岛素的口服吸收，特别是结肠吸收，以Eudragit S100®（ES）壳聚糖纳米粒为载体，研究了胰岛素和反式转录激活肽（达特）在ES壳聚糖纳米粒中的体外释放，发现胰岛素和达特在ES壳聚糖纳米粒中的释放具有pH依赖性。在pH1.2的模拟胃液中，少量的内容物从包衣纳米粒中释放，而在pH7.4的介质中观察到相当快和完全的释放。Caco-2细胞被用作细胞转运和摄取研究的模型。结果表明，共负载胰岛素和达特的ES-壳聚糖纳米粒（ES-达特-cNPs）的细胞转运和摄取胰岛素的能力分别是仅负载胰岛素的纳米粒（ES-cNPs）的3倍和4倍。分别对糖尿病大鼠和正常小型猪进行体内评价。大鼠实验结果表明，ES-Tat-cNPs的药效学生物利用度是ES-cNPs的2.16倍。经口给药后，ES-Tat-cNPs的胰岛素生物利用度是ES-cNPs的1.73倍，并且两种纳米颗粒的胰岛素主要吸收部位可能位于结肠。总之，本报告提供了改善胰岛素口服吸收的探索性方法。
In order to improve oral absorption of insulin, especially the absorption at the colon, Eudragit S100® (ES)-coated chitosan nanoparticles loading insulin and a trans-activating transcriptional peptide (Tat) were employed as the vehicle.In vitroreleases of insulin and Tat from ES-coated chitosan nanoparticles had a pH-dependant characteristic. A small amount of the contents was released from the coated nanoparticles at pH 1.2 simulated gastric fluid, while a fairly fast and complete release was observed in pH 7.4 medium. Caco-2 cell was used as the model of cellular transport and uptake studies. The results showed that the cellular transport and uptake of insulin for ES-coated chitosan nanoparticles co-loading insulin and Tat (ES-Tat-cNPs) were about 3-fold and 4-fold higher than those for the nanoparticles loading only insulin (ES-cNPs), respectively. The evaluationsin vivoof ES-Tat-cNPs were conducted on diabetic rats and normal minipigs, respectively. The experimental results on rats revealed that the pharmacodynamical bioavailability of ES-Tat-cNPs had 2.16-fold increase compared with ES-cNPs. After oral administration of nanoparticle suspensions to the minipigs, insulin bioavailability of ES-Tat-cNPs was 1.73-fold higher than that of ES-cNPs, and the main absorption site of insulin was probably located in the colon for the two nanoparticles. In summary, this report provided an exploratory means for the improvement of oral absorption of insulin.