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Curr Drug Deliv. 2019;16(6):511-529. doi: 10.2174/1567201816666190515105532.

Talazoparib Loaded Solid Lipid Nanoparticles: Preparation, Characterization and Evaluation of the Therapeutic Efficacy In vitro.

Author information

1
Deparment of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, Turkey.
2
Deparment of Medical Biology, Faculty of Medicine, Uludag University, Bursa, Turkey.
3
Central Research Laboratory, Application and Research Center (ARUM), Eskisehir Osmangazi University, Eskisehir, Turkey.

Abstract

OBJECTIVE:

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 4°C.

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.

KEYWORDS:

Apoptosis; PARP inhibitors; Solid Lipid Nanoparticles (SLNs); Talazoparib (BMN 673); Triple Negative Breast Cancer (TNBC); cytotoxic effects.

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