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优化和评估设计用于siRNA口服输送的抗胃微粒
Thomas Stalder1, Nathan Koenig1, Raphaël Cornu2
1Université de Franche-Comté, CHU Besançon, EFS, INSERM, UMR RIGHT, F-25000 Besançon, France.
概括
开发耐胃抗性酸微粒 (MPs) 能够通过口服输送小干扰RNA (siRNA) 治疗肠道疾病. 这些MPs保护敏感的siRNA载脂纳米粒子 (LNPs) 免受胃部的降解,从而保持治疗活性.
科学领域:
- 生物技术是生物技术.
- 药品制造 药品制造 药品制造
- 纳米医学是一种纳米医学.
背景情况:
- 对于肠道疾病的小干扰RNA (siRNA) 口服,由于胃肠道的降解而面临挑战.
- 脂质纳米粒子 (LNPs) 是常见的siRNA载体,易受胃酸,胆盐和消化酶的影响.
研究的目的:
- 设计和评估胃抵抗性酸微粒 (MP) 用于口服输送siRNA.
- 在这些MP中封装siRNA载荷的LNP,包括已销售的产品 (Onpattro®) 和TNF-αsiRNA.
主要方法:
- 使用原始工艺开发酸盐MP,在没有挤出或乳化的情况下达到200微米以下的平均直径.
- 在高效率 (≥80%) 的情况下封装Onpattro®和TNF-α siRNA载荷的LNP.
- 在模拟的胃和肠液中评估胃抵抗和肠道释放.
主要成果:
- 阿尔金纳特国会议员成功地用高效率封装了siRNA载荷的LNP.
- 在模拟的肠道条件下,MPs表现出胃抵抗和受控释放.
- 胃后暴露,含有siRNA的MPs保持了治疗活性,降低了相关细胞系中的基因表达 (基因和TNF-α).
结论:
- 胃抵抗性酸MP是一种可行的策略,可以将口服siRNA输送到肠道.
- 这种配方保护敏感的siRNA载荷的LNP免受降解,保持它们的生物活性.
- 开发的MP具有通过口服siRNA治疗来治疗癌症和炎症性肠病等肠道疾病的潜力.
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