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评估一种新型聚米辛B配方的毒性降低:从3D芯片模型的见解

Anurag Payasi¹, Manoj Kumar Yadav¹, Saransh Chaudhary²

¹Department of Cell Culture, Venus Medicine Research Centre, Baddi, Himachal Pradesh, India.

Antimicrobial agents and chemotherapy

|September 3, 2024

概括

VRP-034,一种新的polymyxin B配方,在3D芯片模型中显示的毒性明显低于标准的polymyxin B. 这种新型配方可能允许更安全地使用全剂量的多素B抗生素.

科学领域:

腎病學和毒理學.
生物标志物发现发现
微生理系统微生理系统

背景情况:

聚米辛B (PMB) 是一种关键的抗生素,用于治疗多抗药性格拉姆阴性细菌感染.
毒性限制了PMB的临床实用性,需要开发更安全的替代品.
三维 (3D) 芯片上的模型为评估药物毒性提供了一个有前途的平台.

研究的目的:

为了比较VRP-034的毒性,一种新的PMB配方,与市场上销售的PMB.
评估损伤,细胞健康和炎症反应,使用3D芯片模型.
为了确定潜在的生物标志物,表明PMB诱导的毒性.

主要方法:

人类脏近道管细胞 (RPTEC/hTERT1) 在三通道芯片中培养,形成管状结构.
细胞被暴露在VRP-034或以各种度 (1-200μM) 销售的PMB中,长达48小时.
确定了损伤生物标志物,细胞活力 (素AM,EthD-1),炎症标志物 (IL-6,IL-8) 和亡标志物 (酶,细胞染色体C) 的数量.

主要成果:

与VRP-034相比,市场上的PMB显著增加了关键损伤生物标志物 (KIM-1,cystatin C,clusterin,OPN),特别是在临床相关度 (≥10μM) 的情况下.
VRP-034表现出优越的细胞健康结果,乳酸脱酶释放率较低,炎症标志物升高 (IL-6,IL-8) 降低.
市场上销售的PMB诱导了更严重的管状损伤和亡,与VRP-034相比,通过更高的酶激活证明了这一点.

结论:

与市场上的PMB相比,VRP-034在3D脏芯片模型中显著降低了毒性.
这种新的配方有可能提高聚米辛B疗法的安全性.
VRP-034可能使得多素B的完整治疗剂量能够被给予,从而解决了对较少毒性抗生素的需求.

关键词:

在VRP-0344中使用.在芯片上的脏微生理系统的微生理系统.毒性毒性毒性聚氨酸B的多种成分靠近的管道靠近的管道

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