道大小扩大策略用于脂质体生产规模扩大:一种简化方法
Simone Bonacorsi1, Lucrezia Angeloni1, Mauro Moliterno2
1Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy; BSP Pharmaceuticals S.p.A., Via Appia Km. 65, 561, 04013 Latina Scalo, LT, Italy.
International journal of pharmaceutics
|September 17, 2025
概括
这项研究提出了一个可扩展的流体系统,使用T形混合器来产生高度均的脂质体. 该方法确保在各种流速中保持一致的颗粒大小和均性,从而使工业规模的纳米医药制造成为可能.
科学领域:
- 纳米技术纳米技术
- 生物医学工程 生物医学工程
- 化学工程是化学工程的重要组成部分.
背景情况:
- 脂质体纳米药物的临床转化受到可扩展生产和精确控制颗粒大小和同质性的挑战的阻碍.
- 微流体为脂质体制造提供单步解决方案,但在工业集成的吞吐量方面面临局限性.
研究的目的:
- 开发和验证一种多功能流体系统,用于使用商用T形混合器可扩展,高吞吐量生产单分散脂质体.
- 调查流量参数 (总流量,雷诺兹数) 对脂质体特征 (大小,多分散性指数) 的影响,并确定可扩展性因子.
主要方法:
- 用于脂质体生产的T形混合器,总流量 (TFR) 从mL/min到30L/h不等.
- 研究了层状和流模式对空Doxil®脂质体大小和多聚分散指数 (PDI) 的影响.
- 通过增加混合器通道大小和TFR,同时保持恒定的雷诺兹数 (Re),以确保一致的流量条件和脂质体属性,扩大了系统规模.
主要成果:
- 通过过渡到流模式,实现了高度单分散的脂质体,提高了同质性和可重复性.
- 证明雷诺兹数 (Re) 是缩放脂质体生产的可靠因素,在Re,粒子大小和PDI之间产生了经验相关性.
- 成功生产了80纳米的Doxil®脂质体,载有大规模的多克索鲁比,由冷传输电子显微镜 (Cryo-TEM) 证实.
- 验证了其他纳米粒子的可扩展性方法,包括空的Marqibo®和DOTAP纳米粒子,显示一致的结果.
结论:
- 开发的流体系统为工业脂质体生产提供了一个可扩展,高效和可适应的战略.
- 这种方法弥合了实验室规模的创新和纳米药物的工业实施之间的差距.
- 通过流体参数来控制脂质体工程,为增强的纳米药物制造提供实用见解.
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