通过可吸入脂质体系统性蛋白质输送:配方和药理动力学
Pranav Ponkshe1, Yingzhe Wang2, Chalet Tan3
1Department of Pharmaceutics and Drug Delivery, University of Mississippi, Oxford, MS 38677, USA.
Pharmaceutics
|July 29, 2023
概括
从五克里斯托酸胆 (DMPC) 制造的可吸入脂质体显示出对全身蛋白质输送的希望. 这些脂质体显著提高了小鼠的生物可用性,并延长了牛血清白蛋白 (BSA) 的停留时间.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 肺部药物输送 肺部药物输送
背景情况:
- 由于其薄薄的结构,膜上皮提供了系统性蛋白质输送的潜在途径.
- 脂类,类似于肺表面活性剂,表现出很好的生物相容性,用于肺部的管理.
研究的目的:
- 设计和优化可吸入脂质体,以进行非侵入性全身蛋白质输送.
- 评估肺部注射后蛋白质载荷脂质体的药理动力学和生物分解.
主要方法:
- 基于dimyristoylphosphatidylcholine (DMPC) 的脂质体的配方具有不同的胆固醇 (Chol) 和聚乙烯甘醇 (PEG) 含量.
- 优化涉及评估封装效率,在模拟的肺液中释放动力学和巨细胞吸收.
- 在小鼠中进行了装载脂质体的Cy5.5标记牛血清白蛋白 (BSA-Cy5.5) 的内气溶剂.
- 血的药理动力学和全身近红外 (NIR) 光成像被用于追踪BSA-Cy5.5生物降解10天.
主要成果:
- 最佳的脂质体组成被确定为DMPC/Chol/PEG,其摩尔比为85:10:5.
- 吸入的脂质体导致BSA-Cy5.5的系统生物利用率为22%,明显高于自由的BSA-Cy5.5.
- 近红外成像证实了通过脂质体传递的BSA-Cy5.5的平均停留时间明显延长.
结论:
- 可吸入的基于DMPC的脂质体是通过肺部途径进行非侵入性全身蛋白质输送的有希望的平台.
- 与免费的蛋白质管理相比,脂质体封装增强了蛋白质的生物可用性,并延长了其在循环中的存在.
- 这种方法为全身蛋白疗法提供了可行的替代方案,绕过了传统的注射方法.
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