Cargando…
The metabolic fate of oxaliplatin in the biological milieu investigated during in vivo lung perfusion using a unique miniaturized sampling approach based on solid-phase microextraction coupled with liquid chromatography-mass spectrometry
Adjuvant chemotherapy after pulmonary metastasectomy for colorectal cancer may reduce recurrence and improve survival rates; however, the benefits of this treatment are limited by the significant side effects that accompany it. The development of a novel in vivo lung perfusion (IVLP) platform would...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9453651/ https://www.ncbi.nlm.nih.gov/pubmed/36092704 http://dx.doi.org/10.3389/fcell.2022.928152 |
_version_ | 1784785188047290368 |
---|---|
author | Olkowicz, Mariola Rosales-Solano, Hernando Ramadan, Khaled Wang, Aizhou Cypel, Marcelo Pawliszyn, Janusz |
author_facet | Olkowicz, Mariola Rosales-Solano, Hernando Ramadan, Khaled Wang, Aizhou Cypel, Marcelo Pawliszyn, Janusz |
author_sort | Olkowicz, Mariola |
collection | PubMed |
description | Adjuvant chemotherapy after pulmonary metastasectomy for colorectal cancer may reduce recurrence and improve survival rates; however, the benefits of this treatment are limited by the significant side effects that accompany it. The development of a novel in vivo lung perfusion (IVLP) platform would permit the localized delivery of high doses of chemotherapeutic drugs to target residual micrometastatic disease. Nonetheless, it is critical to continuously monitor the levels of such drugs during IVLP administration, as lung injury can occur if tissue concentrations are not maintained within the therapeutic window. This paper presents a simple chemical-biopsy approach based on sampling with a small nitinol wire coated with a sorbent of biocompatible morphology and evaluates its applicability for the near-real-time in vivo determination of oxaliplatin (OxPt) in a 72-h porcine IVLP survival model. To this end, the pigs underwent a 3-h left lung IVLP with 3 doses of the tested drug (5, 7.5, and 40 mg/L), which were administered to the perfusion circuit reservoir as a bolus after a full perfusion flow had been established. Along with OxPt levels, the biocompatible solid-phase microextraction (SPME) probes were employed to profile other low-molecular-weight compounds to provide spatial and temporal information about the toxicity of chemotherapy or lung injury. The resultant measurements revealed a rather heterogeneous distribution of OxPt (over the course of IVLP) in the two sampled sections of the lung. In most cases, the OxPt concentration in the lung tissue peaked during the second hour of IVLP, with this trend being more evident in the upper section. In turn, OxPt in supernatant samples represented ∼25% of the entire drug after the first hour of perfusion, which may be attributable to the binding of OxPt to albumin, its sequestration into erythrocytes, or its rapid nonenzymatic biotransformation. Additionally, the Bio-SPME probes also facilitated the extraction of various endogenous molecules for the purpose of screening biochemical pathways affected during IVLP (i.e., lipid and amino acid metabolism, steroidogenesis, or purine metabolism). Overall, the results of this study demonstrate that the minimally invasive SPME-based sampling approach presented in this work can serve as (pre)clinical and precise bedside medical tool. |
format | Online Article Text |
id | pubmed-9453651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94536512022-09-09 The metabolic fate of oxaliplatin in the biological milieu investigated during in vivo lung perfusion using a unique miniaturized sampling approach based on solid-phase microextraction coupled with liquid chromatography-mass spectrometry Olkowicz, Mariola Rosales-Solano, Hernando Ramadan, Khaled Wang, Aizhou Cypel, Marcelo Pawliszyn, Janusz Front Cell Dev Biol Cell and Developmental Biology Adjuvant chemotherapy after pulmonary metastasectomy for colorectal cancer may reduce recurrence and improve survival rates; however, the benefits of this treatment are limited by the significant side effects that accompany it. The development of a novel in vivo lung perfusion (IVLP) platform would permit the localized delivery of high doses of chemotherapeutic drugs to target residual micrometastatic disease. Nonetheless, it is critical to continuously monitor the levels of such drugs during IVLP administration, as lung injury can occur if tissue concentrations are not maintained within the therapeutic window. This paper presents a simple chemical-biopsy approach based on sampling with a small nitinol wire coated with a sorbent of biocompatible morphology and evaluates its applicability for the near-real-time in vivo determination of oxaliplatin (OxPt) in a 72-h porcine IVLP survival model. To this end, the pigs underwent a 3-h left lung IVLP with 3 doses of the tested drug (5, 7.5, and 40 mg/L), which were administered to the perfusion circuit reservoir as a bolus after a full perfusion flow had been established. Along with OxPt levels, the biocompatible solid-phase microextraction (SPME) probes were employed to profile other low-molecular-weight compounds to provide spatial and temporal information about the toxicity of chemotherapy or lung injury. The resultant measurements revealed a rather heterogeneous distribution of OxPt (over the course of IVLP) in the two sampled sections of the lung. In most cases, the OxPt concentration in the lung tissue peaked during the second hour of IVLP, with this trend being more evident in the upper section. In turn, OxPt in supernatant samples represented ∼25% of the entire drug after the first hour of perfusion, which may be attributable to the binding of OxPt to albumin, its sequestration into erythrocytes, or its rapid nonenzymatic biotransformation. Additionally, the Bio-SPME probes also facilitated the extraction of various endogenous molecules for the purpose of screening biochemical pathways affected during IVLP (i.e., lipid and amino acid metabolism, steroidogenesis, or purine metabolism). Overall, the results of this study demonstrate that the minimally invasive SPME-based sampling approach presented in this work can serve as (pre)clinical and precise bedside medical tool. Frontiers Media S.A. 2022-08-25 /pmc/articles/PMC9453651/ /pubmed/36092704 http://dx.doi.org/10.3389/fcell.2022.928152 Text en Copyright © 2022 Olkowicz, Rosales-Solano, Ramadan, Wang, Cypel and Pawliszyn. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Olkowicz, Mariola Rosales-Solano, Hernando Ramadan, Khaled Wang, Aizhou Cypel, Marcelo Pawliszyn, Janusz The metabolic fate of oxaliplatin in the biological milieu investigated during in vivo lung perfusion using a unique miniaturized sampling approach based on solid-phase microextraction coupled with liquid chromatography-mass spectrometry |
title | The metabolic fate of oxaliplatin in the biological milieu investigated during in vivo lung perfusion using a unique miniaturized sampling approach based on solid-phase microextraction coupled with liquid chromatography-mass spectrometry |
title_full | The metabolic fate of oxaliplatin in the biological milieu investigated during in vivo lung perfusion using a unique miniaturized sampling approach based on solid-phase microextraction coupled with liquid chromatography-mass spectrometry |
title_fullStr | The metabolic fate of oxaliplatin in the biological milieu investigated during in vivo lung perfusion using a unique miniaturized sampling approach based on solid-phase microextraction coupled with liquid chromatography-mass spectrometry |
title_full_unstemmed | The metabolic fate of oxaliplatin in the biological milieu investigated during in vivo lung perfusion using a unique miniaturized sampling approach based on solid-phase microextraction coupled with liquid chromatography-mass spectrometry |
title_short | The metabolic fate of oxaliplatin in the biological milieu investigated during in vivo lung perfusion using a unique miniaturized sampling approach based on solid-phase microextraction coupled with liquid chromatography-mass spectrometry |
title_sort | metabolic fate of oxaliplatin in the biological milieu investigated during in vivo lung perfusion using a unique miniaturized sampling approach based on solid-phase microextraction coupled with liquid chromatography-mass spectrometry |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9453651/ https://www.ncbi.nlm.nih.gov/pubmed/36092704 http://dx.doi.org/10.3389/fcell.2022.928152 |
work_keys_str_mv | AT olkowiczmariola themetabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry AT rosalessolanohernando themetabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry AT ramadankhaled themetabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry AT wangaizhou themetabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry AT cypelmarcelo themetabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry AT pawliszynjanusz themetabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry AT olkowiczmariola metabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry AT rosalessolanohernando metabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry AT ramadankhaled metabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry AT wangaizhou metabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry AT cypelmarcelo metabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry AT pawliszynjanusz metabolicfateofoxaliplatininthebiologicalmilieuinvestigatedduringinvivolungperfusionusingauniqueminiaturizedsamplingapproachbasedonsolidphasemicroextractioncoupledwithliquidchromatographymassspectrometry |