Neelesh Kumar Mehra1, Rajeshwar R Tekmal2, Srinath Palakurthi3. 1. Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, U.S.A. 2. Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, U.S.A. 3. Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, U.S.A. palakurthi@pharmacy.tamhsc.edu.
Abstract
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. Copyright
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-6C-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. Copyright
Authors: Junior Gonzales; Susanne Kossatz; Sheryl Roberts; Giacomo Pirovano; Christian Brand; Carlos Pérez-Medina; Patrick Donabedian; M Jason de la Cruz; Willem J M Mulder; Thomas Reiner Journal: Bioconjug Chem Date: 2018-11-07 Impact factor: 4.774