Preparation and in vitro evaluation of doxorubicin-loaded Fe3O4 magnetic nanoparticles modified with biocompatible copolymers
Abolfazl Akbarzadeh1, Haleh Mikaeili2, Nosratollah Zarghami3, Rahmati Mohammad3, Amin Barkhordari3, Soodabeh Davaran2
1Drug Applied Research Center, 2Tuberculosis and Lung Disease Research Center of Tabriz, 3Department of Clinical Biochemistry and Laboratory Medicine, Division of Medical Biotechnology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Background: Superparamagnetic iron oxide nanoparticles are attractive materials that have been widely used in medicine for drug delivery, diagnostic imaging, and therapeutic applications. In our study, superparamagnetic iron oxide nanoparticles and the anticancer drug, doxorubicin hydrochloride, were encapsulated into poly (D, L-lactic-co-glycolic acid) poly (ethylene glycol) (PLGA-PEG) nanoparticles for local treatment. The magnetic properties conferred by superparamagnetic iron oxide nanoparticles could help to maintain the nanoparticles in the joint with an external magnet.
Methods: A series of PLGA:PEG triblock copolymers were synthesized by ring-opening polymerization of D, L-lactide and glycolide with different molecular weights of polyethylene glycol (PEG2000, PEG3000, and PEG4000) as an initiator. The bulk properties of these copolymers were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy, and differential scanning calorimetry. In addition, the resulting particles were characterized by x-ray powder diffraction, scanning electron microscopy, and vibrating sample magnetometry.
Results: The doxorubicin encapsulation amount was reduced for PLGA:PEG2000 and PLGA:PEG3000 triblock copolymers, but increased to a great extent for PLGA:PEG4000 triblock copolymer. This is due to the increased water uptake capacity of the blended triblock copolymer, which encapsulated more doxorubicin molecules into a swollen copolymer matrix. The drug encapsulation efficiency achieved for Fe3O4 magnetic nanoparticles modified with PLGA:PEG2000, PLGA:PEG3000, and PLGA:PEG4000 copolymers was 69.5%, 73%, and 78%, respectively, and the release kinetics were controlled. The in vitro cytotoxicity test showed that the Fe3O4-PLGA:PEG4000 magnetic nanoparticles had no cytotoxicity and were biocompatible.
Conclusion: There is potential for use of these nanoparticles for biomedical application. Future work includes in vivo investigation of the targeting capability and effectiveness of these nanoparticles in the treatment of lung cancer.
Keywords: superparamagnetic iron oxide nanoparticles, triblock copolymer, doxorubicin encapsulation, water uptake, drug encapsulation efficiency
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