Eskiler, Gamze GüneyDikmen, Gökhan2024-05-152024-05-152019Eskiler, G. G. vd. (2019). " Talazoparib loaded solid lipid nanoparticles: Preparation, characterization and evaluation of the therapeutic efficacy in vitro", 16(6), 511-529.1567-2018https://www.eurekaselect.com/article/98496https://hdl.handle.net/11452/41441Objective: In the present work, we report for the first time the therapeutic potential of talazoparib (BMN 673)-SLNs for the treatment of BRCA1 deficient Triple Negative Breast Cancer (TNBC). BMN 673-SLNs were produced by hot-homogenization technique and then characterized. Methods: The cytotoxic and apoptotic effects of BMN 673-SLNs compared with BMN 673 were determined on HCC1937BRCA1-/-, HCC1937-R resistant TNBC and MCF-10A control cell lines. BMN 673- SLNs were found to have reduced particle size (219.5 ± 1.45 nm) and thus more stable (-28.4 ± 2.52 mV) than BMN 673 (1652 ± 2.46 nm and -18.6 ± 0.45 mV) at 4ºC. Results: In vitro cell line studies demonstrated that BMN 673-SLNs showed significant cytotoxic effects on HCC1937 (29.8%) and HCC1937-R cells (35.7%) at 10 nM for 12 days compared with BMN 673 (HCC1937 cells: 34.0% and HCC1937-R cells: 93.8% at 10 nM for 12 days) (p<0.05). Additionally, BMN 673-SLNs (40.1%) reduced the toxicity of BMN 673 (53.1%) on MCF-10A control cells thanks to unique physical properties. Conclusion: The apoptotic rates in the 10 nM BMN 673-SLNs treatment (88.78% and 85.56%) for 12 days were significantly higher than those in 10 nM BMN 673 (82.6% and 25.86%) for 12 days in HCC1937 and HCC1937-R cells, respectively (p<0.01). Furthermore, these effects were consistent with the findings of colony formation, wound healing and calcein accumulation analysis. In conclusion, the therapeutic potential of BMN 673-SLNs provides a promising chemotherapeutic strategy for the treatment of drugresistant TNBC.eninfo:eu-repo/semantics/closedAccessTriple negative breast cancer (TNBC)PARP inhibitorsTalazoparib (BMN 673)Solid lipid nanoparticles (SLNs)ApoptosisCytotoxic effectsDrug-delivery-systemsInhiıbitor Bmn 673Parp InhibitorDNA-repairMultidrug-resistanceSynthetic lethalityHighly potentCancerCytotoxicityPaclitaxelAntineoplastic agentsApoptosisBRCA1 proteinCell proliferationDose-response relationship, drugDrug screening assays, antitumorLipidsNanoparticlesPhthalazinesStructure-activity relationshipTriple negative breast neoplasmsTumorcellsCulturedFemaleArticle0004833869000042-s2.0-8507284906751152916631113350https://doi.org/10.2174/1567201816666190515105532Pharmacology & pharmacyOlaparib; Ovarian Neoplasms; Homologous Recombination