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皮下脂肪体输送改善了单克隆抗体的药理动力学 in vivo

Maryam Karimi¹, Arash Aslanabadi¹, Ben Atkinson¹

¹Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.

Acta biomaterialia

|February 18, 2025

概括

脂质体封装增强了单克隆抗体 (mAbs) 的皮下输送,改善了生物可用性和延长了与传统IV和SC注射相比的半衰期. 这种策略为mAb疗法提供了一种更有效,更为患者友好的方法.

科学领域:

生物技术和制药科学生物技术和制药科学
药物输送系统药物输送系统
免疫学和传染病的研究

背景情况:

单克隆抗体 (mAbs) 是有效的治疗药物,但面临的管理挑战,包括繁的静脉注射 (IV) 交付和较低的生物可用性与皮下 (SC) 管理.
目前的mAbs的SC给药可能会导致由于药理动力学 (PK) 和潜在的免疫性差,有效性降低.
开发改进的mAbs输送方法对于增强其治疗应用至关重要,特别是对于需要重复剂量的慢性疾病.

研究的目的:

评估脂质体配方在改善皮下输送和广泛中和抗体 (bNAbs) 药理学概况方面的疗效.
通过SC和IV途径注射的自由mAbs与体封装的mAbs的PK进行比较.
评估脂质体封装的潜力,以提高对需要持续治疗的疾病的mAbs的治疗效用.

主要方法:

单克隆抗体 (mAbs) 被封装在脂质体中,一些配方包含PEGylation.
脂质体配方的特征是颗粒大小,多分散度指数,泽塔潜力和药物释放动力学.
通过SC和IV途径注射自由mAbs或脂质体封装的mAbs (PEGylated和非PEGylated) 后,在人性化的FcRn小鼠中进行了药理动力学 (PK) 研究.

主要成果:

脂质体配方表现出有利的特性,包括适当的颗粒大小和在4°C的稳定性.
在体内研究表明,与非PEGylated相比,PEGylated脂质体配方通常表现出改善的PK参数 (更高的半衰期,Cmax,AUC,MRT;更低的CL).
与自由mAbs相比,脂质体封装显著增强了SC递送,导致高达113%的生物可用性和比SC自由mAbs更长的半衰期81%,并且在静脉注射后得到改善.

结论:

脂质体封装是一种有效的策略,可以保护SC-administered mAbs免受降解,实现持续释放,并显著改善它们的药理动力学特征.
这种方法提供了一种有希望的方法来增强mAbs的治疗潜力,特别是在需要频繁管理的治疗中.
建议进一步优化脂质体配方,以最大限度地提高负载能力,稳定性和控制释放动力学,以实现先进的mAb输送.

关键词:

半衰期半衰期半衰期脂质细胞体中的脂肪体.单克隆抗体 (mAbs) 是一种单克隆抗体.药理动力学 (PK) 是指药理动力学皮下 (SC) 输送方式

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