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In vitro analysis of PARP inhibitor nanoformulations
- Source :
- International Journal of Nanomedicine
- Publication Year :
- 2018
- Publisher :
- Dove Press, 2018.
-
Abstract
- 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
- Subjects :
- 0301 basic medicine
Drug
PARP-l
Poly ADP ribose polymerase
media_common.quotation_subject
Cell
Short Report
Biophysics
Biological Availability
Pharmaceutical Science
Antineoplastic Agents
Bioengineering
Poly(ADP-ribose) Polymerase Inhibitors
olaparib
BMN-673
Piperazines
Olaparib
Biomaterials
03 medical and health sciences
chemistry.chemical_compound
Drug Delivery Systems
International Journal of Nanomedicine
Cell Line, Tumor
Drug Discovery
DNA Repair Protein
medicine
Transcriptional regulation
Humans
DNA repair protein
media_common
tumor accumulation
Organic Chemistry
General Medicine
Nanostructures
Bioavailability
030104 developmental biology
medicine.anatomical_structure
chemistry
PARP inhibitor
Cancer research
Phthalazines
Subjects
Details
- Language :
- English
- ISSN :
- 11782013
- Database :
- OpenAIRE
- Journal :
- International Journal of Nanomedicine
- Accession number :
- edsair.doi.dedup.....71a933e9cd039e1384dc4b147e4d9fa4