Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ottria, Roberta, Ravelli, Alessandro, Miceli, Matteo, Casati, Sara, Orioli, Marica, Ciuffreda, Pierangela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783405589983920128
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
work_keys_str_mv AT ottriaroberta quantitativecharacterizationofolaparibinnanodeliverysystemandtargetcellcompartmentsbylcmsms
AT ravellialessandro quantitativecharacterizationofolaparibinnanodeliverysystemandtargetcellcompartmentsbylcmsms
AT micelimatteo quantitativecharacterizationofolaparibinnanodeliverysystemandtargetcellcompartmentsbylcmsms
AT casatisara quantitativecharacterizationofolaparibinnanodeliverysystemandtargetcellcompartmentsbylcmsms
AT oriolimarica quantitativecharacterizationofolaparibinnanodeliverysystemandtargetcellcompartmentsbylcmsms
AT ciuffredapierangela quantitativecharacterizationofolaparibinnanodeliverysystemandtargetcellcompartmentsbylcmsms