a EA 3452 CITHÉFOR , Université de Lorraine, Faculté de Pharmacie , Nancy , France.
b INSERM U1256 , Université de Lorraine, Faculté de Médecine , Nancy , France.
Drug Dev Ind Pharm. 2019 Mar;45(3):423-429. doi: 10.1080/03639045.2018.1546313. Epub 2018 Dec 6.
S-nitrosogluthatione (GSNO), a S-nitrosothiol, is a commonly used as nitric oxide (NO) donor. However, its half-life is too short for a direct therapeutic use. To protect and ensure a sustained release of NO, the encapsulation of GSNO into nanoparticles may be an interesting option.
In this work, we have investigated the early (4 h) and late (24 h) transcriptomic response of THP-1 human monocytes cells to two doses (1.4 and 6 µM) of either free or Eudragit nano-encapsulated GSNO using RNA microarray.
After exposure to free GSNO, genes mainly involved in apoptosis, cell differentiation, immune response and metabolic processes were differentially expressed. Although, cells exposed to free or encapsulated GSNO behave differently, activation of genes involved in blood coagulation, immune response and cell cycle was observed in both conditions.
These results suggest that the encapsulation of low doses of GSNO into Eudragit nanoparticles leads to a progressive release of GSNO making this compound a possible oral therapy for several biomedical applications like inflammatory bowel diseases.
S-亚硝基谷胱甘肽(GSNO)是一种常用的一氧化氮(NO)供体。然而,由于其半衰期太短,无法直接用于治疗。为了保护并确保 NO 的持续释放,将 GSNO 封装成纳米颗粒可能是一种有趣的选择。
在这项工作中,我们使用 RNA 微阵列研究了 THP-1 人单核细胞在暴露于两种剂量(1.4 和 6 μM)游离或 Eudragit 纳米封装 GSNO 4 小时(早期)和 24 小时(晚期)时的早期和晚期转录组反应。
暴露于游离 GSNO 后,主要涉及细胞凋亡、细胞分化、免疫反应和代谢过程的基因表达差异。尽管暴露于游离或封装的 GSNO 的细胞表现不同,但在两种情况下均观察到参与血液凝固、免疫反应和细胞周期的基因被激活。
这些结果表明,将低剂量的 GSNO 封装到 Eudragit 纳米颗粒中会导致 GSNO 的逐渐释放,使该化合物成为几种生物医学应用(如炎症性肠病)的口服治疗药物成为可能。