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Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS
Olaparib, an orally active inhibitor of poly(ADP-ribose)polymerase(PARP), is the drug of choice in the treatment of gBRCA1/2+ metastatic breast cancers. Unfortunately, Olaparib is poorly soluble with low bioavailability and tumor accumulation; nano-delivery could be a good choice to overcome these d...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429415/ https://www.ncbi.nlm.nih.gov/pubmed/30862103 http://dx.doi.org/10.3390/molecules24050989 |
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author | Ottria, Roberta Ravelli, Alessandro Miceli, Matteo Casati, Sara Orioli, Marica Ciuffreda, Pierangela |
author_facet | Ottria, Roberta Ravelli, Alessandro Miceli, Matteo Casati, Sara Orioli, Marica Ciuffreda, Pierangela |
author_sort | Ottria, Roberta |
collection | PubMed |
description | Olaparib, an orally active inhibitor of poly(ADP-ribose)polymerase(PARP), is the drug of choice in the treatment of gBRCA1/2+ metastatic breast cancers. Unfortunately, Olaparib is poorly soluble with low bioavailability and tumor accumulation; nano-delivery could be a good choice to overcome these disadvantages. Here, a rapid and robust HPLC-ESI–MS/MS method for the quantification of Olaparib in ferritin nano-carriers led to the development of cells compartments, different tissues, plasma and urines and were validated to assess the effects of nano-delivery on cell compartment distribution of the drug. This method allows the quantification of Olaparib within the linear range of 0.1–10ng/mL in cells culture medium and cell cytoplasm, of 0.5–10ng/mL in nuclei, of 0.5–100ng/mL in plasma and urine and of 10–500ng/mL in tissue samples (kidney and liver). The limit of quantification was found to be 1.54 ng/mL for liver, 2.87 ng/mL for kidney, and lower than 0.48 ng/mL for all matrices. The method has been applied to quantify Ola encapsulated in ferritin-nano-carriers during the nano-drug development. The application of the method to human BRCA-mutated cell model to quantify the Olaparib distribution after incubation of free or ferritin-encapsulated Olaparib is also reported. This sensitive method allows the quantification of low concentrations of Olaparib released from nano-carriers in different cell compartments, leading to the determination of the drug release and kinetic profile of an essential parameter to validate nano-carriers. |
format | Online Article Text |
id | pubmed-6429415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64294152019-04-15 Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS Ottria, Roberta Ravelli, Alessandro Miceli, Matteo Casati, Sara Orioli, Marica Ciuffreda, Pierangela Molecules Article Olaparib, an orally active inhibitor of poly(ADP-ribose)polymerase(PARP), is the drug of choice in the treatment of gBRCA1/2+ metastatic breast cancers. Unfortunately, Olaparib is poorly soluble with low bioavailability and tumor accumulation; nano-delivery could be a good choice to overcome these disadvantages. Here, a rapid and robust HPLC-ESI–MS/MS method for the quantification of Olaparib in ferritin nano-carriers led to the development of cells compartments, different tissues, plasma and urines and were validated to assess the effects of nano-delivery on cell compartment distribution of the drug. This method allows the quantification of Olaparib within the linear range of 0.1–10ng/mL in cells culture medium and cell cytoplasm, of 0.5–10ng/mL in nuclei, of 0.5–100ng/mL in plasma and urine and of 10–500ng/mL in tissue samples (kidney and liver). The limit of quantification was found to be 1.54 ng/mL for liver, 2.87 ng/mL for kidney, and lower than 0.48 ng/mL for all matrices. The method has been applied to quantify Ola encapsulated in ferritin-nano-carriers during the nano-drug development. The application of the method to human BRCA-mutated cell model to quantify the Olaparib distribution after incubation of free or ferritin-encapsulated Olaparib is also reported. This sensitive method allows the quantification of low concentrations of Olaparib released from nano-carriers in different cell compartments, leading to the determination of the drug release and kinetic profile of an essential parameter to validate nano-carriers. MDPI 2019-03-11 /pmc/articles/PMC6429415/ /pubmed/30862103 http://dx.doi.org/10.3390/molecules24050989 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ottria, Roberta Ravelli, Alessandro Miceli, Matteo Casati, Sara Orioli, Marica Ciuffreda, Pierangela Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS |
title | Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS |
title_full | Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS |
title_fullStr | Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS |
title_full_unstemmed | Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS |
title_short | Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS |
title_sort | quantitative characterization of olaparib in nanodelivery system and target cell compartments by lc-ms/ms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429415/ https://www.ncbi.nlm.nih.gov/pubmed/30862103 http://dx.doi.org/10.3390/molecules24050989 |
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