通过充电可逆脂质纳米粒子增强口服胰岛素的输送
Dai Oyama1, Katsuki Matayoshi2, Soya Kanetaka2
1Laboratory of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan; PPM JP1, CMC Product Management, Astellas Pharma Inc., 2-5-1 Nihonbashi-Honcho, Chuo-ku, Tokyo, 103-8411, Japan.
Biochemical and biophysical research communications
|February 1, 2025
概括
这项研究开发了一种用于口服胰岛素输送的新型脂质纳米粒子 (LNP) 系统. 新系统在糖尿病小鼠中有效降低血糖,为胰岛素注射提供了有希望的替代方案.
科学领域:
- 生物技术是生物技术.
- 药物运输 药物运输 药物运输
- 纳米医学是一种纳米医学.
背景情况:
- 口服胰岛素通过模仿自然途径,比注射提供了优势.
- 脂质纳米颗粒 (LNP) 由于其特性,对口服胰岛素有希望,但面临毒性和低生物可用性等挑战.
- 二氧化基甘油酸二乙烯胺 (DOP-DEDA) 是一种对pH反应的脂质,用于细胞质的输送.
研究的目的:
- 开发一种高度生物相容和高效的口服胰岛素输送系统,使用基于DOP-DEDA的LNP.
- 评估开发的胰岛素载荷LNP (Ins-LNP) 的稳定性,胰岛素保留和体内疗效.
主要方法:
- 胰岛素被封装在基于DOP-DEDA的LNP (Ins-LNP) 中.
- PEGylated Ins-LNPs的特征是粒子大小,多分散性和封装效率.
- 在模拟的胃肠液中评估稳定性,在不同的pH水平下测量胰岛素保留率.
- 在体内研究中,在链素诱导的糖尿病小鼠中进行了评估低血糖影响的研究.
主要成果:
- PEGylated Ins-LNPs显示出最佳的颗粒特性和高封装效率.
- 在模拟的胃肠道条件和持续的胰岛素释放中,Ins-LNPs表现出稳定性.
- Ins-LNPs表现出pH依赖的充电行为,表明在胃中的稳定性和在肠道中的吸收.
- 在糖尿病小鼠中,口服Ins-LNPs导致血糖水平在超过10小时内显著且持续下降.
结论:
- 开发的基于DOP-DEDA的LNP系统是有效和生物相容的口服胰岛素输送的有希望的平台.
- 该系统的有利的药学动力学特征表明,有可能改善患者的服药性和治疗结果.
- 这种LNP系统解决了口服胰岛素的关键挑战,为非侵入性治疗策略铺平了道路.
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