Title:Liposomal Doxorubicin Kinetic Study in an In vitro 2D and 3D Tumor
Model for Osteosarcoma in a Perfusion Bioreactor
Volume: 11
Issue: 5
Author(s): H. Abdollahzadeh, G. Amoabediny*, F. Haghiralsadat, F. Rahimi and A. Adibfar
Affiliation:
- Department of Biotechnology and Pharmaceutical Engineering, School of Chemical Engineering, College of Engineering,
University of Tehran, Tehran, Iran
- Department of Biomedical Engineering, Research Center for New Technologies
in Life Science Engineering at the University of Tehran, Tehran, Iran
Keywords:
Liposome, static tumor model, perfusion bioreactor, IVIVC, drug resistance, 3D environment.
Abstract:
Background: In vivo drug screening in animal models is contrary to ethical values, costly
and time-consuming. Traditional static in vitro models do not reflect the basic characteristics of bone
tumor microenvironments; therefore, perfusion bioreactors, in particular, would be an applicable choice
due to their advantages to regenerate versatile bone tumor models for studying in vitro novel drug delivery
systems.
Methods: In this study, an optimal drug formulation of liposomal doxorubicin was prepared, and the release
kinetics of the drug and its toxicity effect on MG-63 bone cancer cell line were investigated in
two-dimensional, static three-dimensional media on a PLGA/β-TCP scaffold and also in a dynamic media
in a perfusion bioreactor. In this assay, the efficacy of the IC50 of this formulation which had been
obtained in two-dimensional cell culture (= 0.1 μg/ml), was studied in static and dynamic threedimensional
media after 3 and 7 days. Liposomes with good morphology and encapsulation efficiency
of 95% had release kinetics of the Korsmeyer-Peppas model.
Results: The results of cell growth before treatment and cell viability after treatment in all three environments
were compared. Cell growth in 2D was rapid, while it was slow in static 3D conditions. In the
dynamic 3D environment, it was significant compared to the static tumor models. Cell viability after 3
and 7 days from treatment was 54.73% and 13.39% in 2D conditions, 72.27% and 26.78% in the static
3D model, while 100% and 78.92% in the dynamic culture indicating the effect of drug toxicity over
time, but drug resistance of 3D models compared to 2D culture. In the bioreactor, the formulation used
in the mentioned concentration showed very small cytotoxicity demonstrating the dominance of mechanical
stimuli on cell growth over drug toxicity.
Conclusion: Increasing drug resistance in 3D models compared to 2D models indicates the superiority
of liposomal Dox over free form to reduce IC50 concentration.
