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Solid phase microextraction chemical biopsy tool for monitoring of doxorubicin residue during in vivo lung chemo-perfusion
Journal of Pharmaceutical Analysis ( IF 6.1 ) Pub Date : 2020-09-02 , DOI: 10.1016/j.jpha.2020.08.011
Barbara Bojko , Nikita Looby , Mariola Olkowicz , Anna Roszkowska , Bogumiła Kupcewicz , Pedro Reck des Santos , Khaled Ramadan , Shaf Keshavjee , Thomas K. Waddell , German Gómez-Ríos , Marcos Tascon , Krzysztof Goryński , Marcelo Cypel , Janusz Pawliszyn

Development of a novel in vivo lung perfusion (IVLP) procedure allows localized delivery of high-dose doxorubicin (DOX) for targeting residual micrometastatic disease in the lungs. However, DOX delivery via IVLP requires careful monitoring of drug level to ensure tissue concentrations of this agent remain in the therapeutic window. A small dimension nitinol wire coated with a sorbent of biocompatible morphology (Bio-SPME) has been clinically evaluated for in vivo lung tissue extraction and determination of DOX and its key metabolites. The in vivo Bio-SPME-IVLP experiments were performed on pig model over various (150 and 225 mg/m2) drug doses, and during human clinical trial. Two patients with metastatic osteosarcoma were treated with a single 5 and 7 μg/mL (respectively) dose of DOX during a 3-h IVLP. In both pig and human cases, DOX tissue levels presented similar trends during IVLP. Human lung tissue concentrations of drug ranged between 15 and 293 μg/g over the course of the IVLP procedure. In addition to DOX levels, Bio-SPME followed by liquid chromatography-mass spectrometry analysis generated 64 metabolic features during endogenous metabolite screening, providing information about lung status during drug administration. Real-time monitoring of DOX levels in the lungs can be performed effectively throughout the IVLP procedure by in vivo Bio-SPME chemical biopsy approach. Bio-SPME also extracted various endogenous molecules, thus providing a real-time snapshot of the physiology of the cells, which might assist in the tailoring of personalized treatment strategy.



中文翻译:

固相微萃取化学活检工具,用于监测体内肺化学灌注过程中的阿霉素残留

新的体内肺灌注(IVLP)程序的开发允许局部递送高剂量的阿霉素(DOX),以靶向肺中残留的微转移性疾病。但是,通过IVLP进行DOX递送需要仔细监测药物水平,以确保该药物的组织浓度保持在治疗范围内。临床上已经评估了涂覆有生物相容性形态吸附剂(Bio-SPME)的小尺寸镍钛诺线材,用于体内肺组织提取和DOX及其关键代谢产物的测定。在各种(150和225 mg / m 2)猪模型上进行了体内Bio-SPME-IVLP实验)的药物剂量,以及在人类临床试验中的剂量。在3小时的IVLP期间,分别用5和7μg/ mL的DOX剂量治疗了2例转移性骨肉瘤患者。在猪和人的情况下,IVLP期间DOX组织水平呈现相似的趋势。在IVLP过程中,人肺组织中药物的浓度范围为15至293μg/ g。除DOX水平外,Bio-SPME随后进行液相色谱-质谱分析,在内源性代谢物筛选过程中还产生了64种代谢特征,从而提供了药物给药过程中有关肺部状态的信息。通过体内Bio-SPME化学活检方法,可以在整个IVLP程序中有效地实时监测肺中DOX的水平。Bio-SPME还提取了各种内源性分子,

更新日期:2020-09-02
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