In vitro analysis of PARP inhibitor nanoformulations

Paige Baldwin,1 Shifalika Tangutoori,1,2 Srinivas Sridhar1,2 1Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USA; 2Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, USA Abstract: PARP-l is a DNA repair protein that plays a role in a numbe...

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Autores principales:	Baldwin P, Tangutoori S, Sridhar S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	PARPl Olaparib BMN-673 DNA repair protein Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5f6d8cd0e01943c2a743e1b6e2b71fde
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spelling	oai:doaj.org-article:5f6d8cd0e01943c2a743e1b6e2b71fde2021-12-02T04:51:13ZIn vitro analysis of PARP inhibitor nanoformulations1178-2013https://doaj.org/article/5f6d8cd0e01943c2a743e1b6e2b71fde2018-03-01T00:00:00Zhttps://www.dovepress.com/in-vitro-analysis-of-parp-inhibitor-nanoformulations-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Paige Baldwin,1 Shifalika Tangutoori,1,2 Srinivas Sridhar1,2 1Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USA; 2Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, USA Abstract: PARP-l is a DNA repair protein that plays a role in a number of repair pathways and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an accumulation of deleterious mutations leading to genetic instability as a result of a number of cell replications. Currently, olaparib is only available in an oral form and has poor bioavailability, consequently leading to poor accumulation in the tumor due to first-pass metabolism. Therefore, in the present study, an injectable nanoparticle formulation of olaparib was created that offers a delivery route in which the drug would be fully bioavailable in the vasculature, suggesting greater tumor accumulation. Our results illustrated that injectable nanoformulations of olaparib and BMN-673, a next generation PARPi, could be developed, and an efficacy test indicated that BMN-673 is a much more potent PARPi than olaparib. The success of these molecular inhibitors as a monotherapy in inhibiting colony formation suggests enhanced efficacy of these treatments in combination with other therapies, even in tumors which have developed resistance. Keywords: PARP-l, olaparib, BMN-673, DNA repair protein, tumor accumulationBaldwin PTangutoori SSridhar SDove Medical PressarticlePARPlOlaparibBMN-673DNA repair proteinMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 59-61 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	PARPl Olaparib BMN-673 DNA repair protein Medicine (General) R5-920
spellingShingle	PARPl Olaparib BMN-673 DNA repair protein Medicine (General) R5-920 Baldwin P Tangutoori S Sridhar S In vitro analysis of PARP inhibitor nanoformulations
description	Paige Baldwin,1 Shifalika Tangutoori,1,2 Srinivas Sridhar1,2 1Nanomedicine Science and Technology Center, Northeastern University, Boston, MA, USA; 2Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA, USA Abstract: PARP-l is a DNA repair protein that plays a role in a number of repair pathways and also helps in transcriptional regulation; thus PARP inhibitors (PARPi), such as olaparib and BMN-673, act by inhibiting DNA damage repair. This leads to an accumulation of deleterious mutations leading to genetic instability as a result of a number of cell replications. Currently, olaparib is only available in an oral form and has poor bioavailability, consequently leading to poor accumulation in the tumor due to first-pass metabolism. Therefore, in the present study, an injectable nanoparticle formulation of olaparib was created that offers a delivery route in which the drug would be fully bioavailable in the vasculature, suggesting greater tumor accumulation. Our results illustrated that injectable nanoformulations of olaparib and BMN-673, a next generation PARPi, could be developed, and an efficacy test indicated that BMN-673 is a much more potent PARPi than olaparib. The success of these molecular inhibitors as a monotherapy in inhibiting colony formation suggests enhanced efficacy of these treatments in combination with other therapies, even in tumors which have developed resistance. Keywords: PARP-l, olaparib, BMN-673, DNA repair protein, tumor accumulation
format	article
author	Baldwin P Tangutoori S Sridhar S
author_facet	Baldwin P Tangutoori S Sridhar S
author_sort	Baldwin P
title	In vitro analysis of PARP inhibitor nanoformulations
title_short	In vitro analysis of PARP inhibitor nanoformulations
title_full	In vitro analysis of PARP inhibitor nanoformulations
title_fullStr	In vitro analysis of PARP inhibitor nanoformulations
title_full_unstemmed	In vitro analysis of PARP inhibitor nanoformulations
title_sort	in vitro analysis of parp inhibitor nanoformulations
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/5f6d8cd0e01943c2a743e1b6e2b71fde
work_keys_str_mv	AT baldwinp invitroanalysisofparpinhibitornanoformulations AT tangutooris invitroanalysisofparpinhibitornanoformulations AT sridhars invitroanalysisofparpinhibitornanoformulations
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In vitro analysis of PARP inhibitor nanoformulations

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