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双功能的半孔性二氧化纳米颗粒用于局部向眼睛后部部段输送阿西替尼
Li Xu1, Zih-An Chen2, Cheng-Hsun Wu3
1Graduate Institute of Nanomedicine and Medical Engineering, Taipei Medical University, Taipei 11031, Taiwan.
概括
新的眼滴使用纳米颗粒向视网膜输送阿克西替尼 (AXT),绕过注射治疗潮湿的与年龄相关的黄斑变性 (AMD). 这种非侵入性方法显示了有效和安全的后眼药物输送的希望.
科学领域:
- 眼科医生 眼科 眼科
- 纳米技术 纳米技术
- 药物运输 药物运输 药物运输
背景情况:
- 局部药物输送到后眼受到解剖学障碍的阻碍.
- 湿时与年龄相关的黄斑变性 (AMD) 治疗通常需要频繁的静脉内注射.
- 现有的治疗需要侵入性手术,这对患者的遵守和安全构成了挑战.
研究的目的:
- 开发一种非侵入性的局部眼滴配方,用于向眼部后部部部位输送阿克西替尼 (AXT).
- 为增强视网膜药物输送设计双功能的半孔化纳米粒子 (AXT@dual-MSNs).
- 为了评估AXT@dual-MSN眼药的疗效和安全性,作为湿 AMD 内注射的替代品.
主要方法:
- 配制25纳米双功能的半孔性二氧化纳米粒子 (AXT@dual-MSNs) 封装阿克西替尼 (AXT).
- 纳米粒子功能化包括硫酸盐组用于药物加载和PEGylated/四级氨基修饰用于稳定性和封闭性.
- 在激光诱导胆道新血管化 (CNV) 的小鼠模型中进行评估,评估视网膜积累,药理动力学和治疗疗效,与免费药物眼滴和静脉内AXT相比.
主要成果:
- AXT@dual-MSNs通过结膜 - 结膜 - 胆膜通路实现了有效的视网膜积累,绕过角膜.
- 药物动力学分析表明,快速的跨膜输送与治疗相关的视网膜AXT度.
- AXT@dual-MSN眼滴在小鼠中显著抑制了中枢神经病毒病变的形成,优于其他输送方法,并显示出出色的眼睛耐受性.
结论:
- 一个新的纳米载体系统 (AXT@dual-MSNs) 能够在眼睛后部部段进行非侵入性局部药物输送.
- 这种配方提供了一种安全,有效和临床可转换的替代方案,用于湿湿的AMD的静脉内注射.
- AXT@dual-MSNs的模块化设计可以适应向视网膜输送其他治疗药物.
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