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

Author(s): Gamze Guney Eskiler*, Gulsah Cecener, Gokhan Dikmen, Unal Egeli, Berrin Tunca.

Journal Name: Current Drug Delivery

Volume 16 , Issue 6 , 2019

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Graphical Abstract:


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

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VOLUME: 16
ISSUE: 6
Year: 2019
Page: [511 - 529]
Pages: 19
DOI: 10.2174/1567201816666190515105532

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