TY - JOUR
T1 - Development and evaluation of talazoparib nanoemulsion for systemic therapy of BRCA1-mutant cancer
AU - Mehra, Neelesh Kumar
AU - Tekmal, Rajeshwar R.
AU - Palakurthi, Srinath
N1 - Publisher Copyright:
© 2018 International Institute of Anticancer Research. All rights reserved.
PY - 2018/8
Y1 - 2018/8
N2 - Aim: This is a debut study report on talazoparib (BMN-673)-loaded nanoemulsion (TZNE) for parenteral administration. Materials and Methods: TZNE (0.05% drug, 151.4±0.7 nm droplet size, polydispersity index of 0.120±0.010 and zeta potential of -33.30±1.22 mV) was designed, developed and characterized using in vitro studies. A cumulative in vitro release study was performed in physiological phosphate buffer solution at different pH (5.3, 6.5 and 7.4) using a dialysis method. Cytotoxicity and apoptosis assays were performed on MDA-MB-231, NCI/ADR-RES, 2008 C13, CP-70 and SKOV-3 cell lines using CellTiter® Blue. Quantitative and qualitative cell uptake was studied using fluorescent probe, coumarin-6 (C-6). Results: The drug release form TZNE nanoemulsion was slow and sustained for 24 h. Cytotoxicity and apoptosis were found to be concentration-dependent. The half-maximal inhibitory concentration of TZNE was 0.4852 and 1.35, 11.757 and 0.4696, and 1.169 and 0.7235 μM in MDA-MB-231, SKOV-3 and NCI/ADR-RES cells with 48 and 72 h incubation, respectively. Cellular uptake studies using fluorescent probe, coumarin-6 C-6, showed higher cellular uptake of TNZE compared with free C6. Results suggest that nanoemulsion could provide a new platform for systemic delivery of talazoparib.
AB - Aim: This is a debut study report on talazoparib (BMN-673)-loaded nanoemulsion (TZNE) for parenteral administration. Materials and Methods: TZNE (0.05% drug, 151.4±0.7 nm droplet size, polydispersity index of 0.120±0.010 and zeta potential of -33.30±1.22 mV) was designed, developed and characterized using in vitro studies. A cumulative in vitro release study was performed in physiological phosphate buffer solution at different pH (5.3, 6.5 and 7.4) using a dialysis method. Cytotoxicity and apoptosis assays were performed on MDA-MB-231, NCI/ADR-RES, 2008 C13, CP-70 and SKOV-3 cell lines using CellTiter® Blue. Quantitative and qualitative cell uptake was studied using fluorescent probe, coumarin-6 (C-6). Results: The drug release form TZNE nanoemulsion was slow and sustained for 24 h. Cytotoxicity and apoptosis were found to be concentration-dependent. The half-maximal inhibitory concentration of TZNE was 0.4852 and 1.35, 11.757 and 0.4696, and 1.169 and 0.7235 μM in MDA-MB-231, SKOV-3 and NCI/ADR-RES cells with 48 and 72 h incubation, respectively. Cellular uptake studies using fluorescent probe, coumarin-6 C-6, showed higher cellular uptake of TNZE compared with free C6. Results suggest that nanoemulsion could provide a new platform for systemic delivery of talazoparib.
KW - BRCA1
KW - Breast cancer
KW - Cell uptake
KW - Cytotoxicity
KW - Nanoemulsion
KW - Talazoparib
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U2 - 10.21873/anticanres.12753
DO - 10.21873/anticanres.12753
M3 - Article
C2 - 30061215
AN - SCOPUS:85050817516
SN - 0250-7005
VL - 38
SP - 4493
EP - 4503
JO - Anticancer Research
JF - Anticancer Research
IS - 8
ER -