Autor: |
Kovshova T; D. Mendeleev University of Chemical Technology of Russia, Moscow, Russia., Mantrov S; D. Mendeleev University of Chemical Technology of Russia, Moscow, Russia., Boiko S; D. Mendeleev University of Chemical Technology of Russia, Moscow, Russia., Malinovskaya J; D. Mendeleev University of Chemical Technology of Russia, Moscow, Russia., Merkulova M; D. Mendeleev University of Chemical Technology of Russia, Moscow, Russia., Osipova N; D. Mendeleev University of Chemical Technology of Russia, Moscow, Russia., Moiseeva N; N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia., Akimov M; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia., Dudina P; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia., Senchikhin I; Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Moscow, Russia., Ermolenko Y; D. Mendeleev University of Chemical Technology of Russia, Moscow, Russia., Gelperina S; D. Mendeleev University of Chemical Technology of Russia, Moscow, Russia. |
Abstrakt: |
The aims of this study were to develop co-delivery systems of paclitaxel (PTX) and etoposide prodrug (4'-O-benzyloxycarbonyl-etoposide, ETP-cbz) based on non-cross-linked human serum albumin (HSA) and poly(lactide-co-glycolide) nanoparticles and to evaluate the synergistic potential of these drugs in vitro . The nanoformulations were prepared by the high-pressure homogenisation technique and characterised using DLS, TEM, SEM, AFM, HPLC, CZE, in-vitro release, and cytotoxicity in human and murine glioma cells. All nanoparticles had 90-150 nm in size and negative ζ-potentials. The Neuro2A cells were the most sensitive to both HSA- and PLGA-based co-delivery systems (IC 50 0.024 µM and 0.053 µM, respectively). The drugs' synergistic effect (combination index < 0.9) was observed in the GL261 cells for both types of co-delivery formulations and in the Neuro2A cells for the HSA-based system. These nanodelivery systems may be useful to improve combination chemotherapy for brain tumour treatment. To our knowledge, this is the first report describing the non-cross-linked HSA-based co-delivery nanosuspension which was prepared using nab™ technology. |