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红细胞中生物治疗药物高阶结构的核磁共振评估为药物递送设计提供了一种工具。

NMR Assessment of the High Order Structure of Biological Therapeutics in Erythrocytes Provides a Tool for Drug Delivery Design.

作者信息

Padilla-Cortés Luis, Gheorghita Giulia Roxana, Currò Francesco, Calamandrei Rebecca, Susini Bianca, Callozzo Sara, Crivello Giulia, Russomanno Pasquale, Ravera Enrico, Cerofolini Linda, Fragai Marco

机构信息

Department of Chemistry Ugo Schiff (DICUS), University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.

Centro di Risonanze Magnetiche (CERM), University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy.

出版信息

J Am Chem Soc. 2025 Jul 30;147(30):26379-26388. doi: 10.1021/jacs.5c05617. Epub 2025 Jul 16.

DOI:10.1021/jacs.5c05617
PMID:40668205
Abstract

An effective delivery system is crucial for ensuring the therapeutic efficacy of a drug. This is especially true for biological drugs, which possess unique physicochemical properties and complex pharmacokinetic profiles, and thus require a dedicated design. Whole erythrocytes, and more recently, nanoparticles derived from red blood cells (RBCs), have been used in preclinical studies to deliver biological therapeutics: their biocompatibility and extended circulation time help prevent immunogenicity and reduce clearance and toxicity. However, characterizing such complex systems poses challenges that complicate their development and optimization. We argue that NMR spectroscopy enables the monitoring of the preservation of the high order structure of the encapsulated proteins, as well as their concentration, thereby assisting in formulation design, development, and manufacturing.

摘要

一个有效的递送系统对于确保药物的治疗效果至关重要。对于生物药物而言尤其如此,生物药物具有独特的物理化学性质和复杂的药代动力学特征,因此需要专门的设计。全红细胞以及最近从红细胞(RBC)衍生而来的纳米颗粒已用于临床前研究以递送生物治疗剂:它们的生物相容性和延长的循环时间有助于防止免疫原性并减少清除率和毒性。然而,表征此类复杂系统带来了挑战,使它们的开发和优化变得复杂。我们认为核磁共振波谱能够监测包封蛋白的高阶结构的保留情况及其浓度,从而有助于制剂的设计、开发和制造。

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本文引用的文献

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biophysical characterization of high-concentration protein formulations using NMR.使用 NMR 对高浓度蛋白质制剂进行生物物理特性分析。
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Integration of NMR Spectroscopy in an Analytical Workflow to Evaluate the Effects of Oxidative Stress on Abituzumab: Beyond the Fingerprint of mAbs.
将 NMR 光谱学集成到分析工作流程中,以评估氧化应激对阿替珠单抗的影响:超越单抗的指纹图谱。
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Preclinical and clinical developments in enzyme-loaded red blood cells: an update.酶负载红细胞的临床前和临床进展:更新。
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Erythrocyte-based Drug Delivery: How Far from Clinical Application?基于红细胞的药物递送:离临床应用还有多远?
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Advances in Drug Delivery Systems Based on Red Blood Cells and Their Membrane-Derived Nanoparticles.基于红细胞及其膜衍生纳米颗粒的药物递送系统研究进展
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