以pH为依赖的蛋白质化学降解作为在聚合物基持续释放配方中的蛋白质周围有效pH的表示
Caroline Black1, Sean McCarthy2, Milad Khorrami1
1Drug Delivery Sciences, AbbVie Inc., Irvine, CA 92612, USA.
Journal of pharmaceutical sciences
|August 18, 2025
概括
这项研究开发了一种新的方法来确定持续释放 (SR) 配方中蛋白质疗法周围的pH环境. 这些发现揭示了不同类型的SR不同的pH值范围,这对于药物稳定性至关重要.
科学领域:
- 生物制药学分析分析
- 药物输送系统是药物输送系统.
- 蛋白质化学 蛋白质化学
背景情况:
- 基于蛋白质的治疗药物容易受到pH驱动的降解.
- 了解持续释放 (SR) 配方中的微环境pH值对于评估治疗适用性和稳定性至关重要.
- 目前在复杂配方中评估in-situ pH的方法有限.
研究的目的:
- 开发和验证一种推断SR配方中蛋白质所经历的pH值的方法.
- 使用模型抗体,描述PLGA微球和氨酸水凝中的pH微环境.
- 建立一种普遍适用的方法,用于蛋白质载荷SR系统的pH表征.
主要方法:
- 使用模型抗体 (mAb1) 的pH敏感化学降解反应作为pH指标.
- 从PLGA微球和不同释放阶段的氨酸水凝中获取分析的mAb1.
- 量化单体含量 (SEC),电荷变异 (icIEF) 和残留水平降解 (图) 的变化,以推断局部pH值.
主要成果:
- mAb1表现出与特定的pH值范围相关的独特化学降解概况.
- 在PLGA微球中,mAb1的推断pH值约为4-7 .
- 在氨酸水凝中,mAb1的推断pH值约为6-7 .
结论:
- 蛋白质的化学反应性可以有效地利用在SR配方中确定其局部pH值.
- PLGA微球和氨酸水凝为蛋白质治疗提供了不同的pH微环境.
- 这种创新方法为评估各种SR配方对蛋白质药物输送的适用性提供了广泛的适用性.
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