Nima Hamzian - Department of Medical Physics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Mohammad Ramezani - Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Maryam Hashemi - Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Mahdi Ghorbani - Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mohammad Hossein Bahreyni Toosi - Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract The aim of this study was to develop a novel multifunctional nanoparticle, which encapsulates SPION and Gemcitabine in PLGA±PEG to form multifunctional drug delivery system. For this aim, super paramagnetic iron oxide nanoparticles (SPIONs) were synthesized and encapsulated simultaneously with Gemcitabine (Gem) in PLGA±PEG copolymers via W/O/W double emulsification method. Optimum size and encapsulation efficiency for radiosensitization, hyperthermia and diagnostic applications were considered and the preparation parameters were systematically investigated and physicochemical characteristics of optimized nanoparticle were studied. Then SPION-PLGA and PLGA-Gem nanoparticles were prepared with the same optimized parameters and the toxicity of these nanoparticles was compared with Gemcitabine in human breast cancer cell line (MCF-۷). The optimum preparation parameters were obtained with Gem/polymer equal to ۰.۰۴, SPION/polymer equal to ۰.۸ and ۱% sucrose per ۲۰ mg of polymer. The hydrodynamic diameters of all nanoparticles were under ۲۰۰ nm. Encapsulation efficiency was adjusted between ۱۳.۲% to ۱۶.۱% for Gemcitabine and ۴۸.۲% to ۵۰.۱% for SPION. In-vitro Gemcitabine release kinetics had controlled behavior. Enhancement ratios for PLGA-Gem and SPION-PLGA-Gem at concentration of nanoparticles equal to IC۵۰ of Gemcitabine were ۱.۵۳ and ۱.۸۹ respectively. The statistical difference was significant (p-value=۰.۰۰۶ for SPION-PLGA-Gem and p-value=۰.۰۱۵ for PLGA-Gem compared with Gemcitabine). In conclusion, we have successfully developed a Gemcitabine loaded super paramagnetic PLGA- Iron Oxide multifunctional drag delivery system. Future work includes in-vitro and in-vivo  investigation of radiosensitization and other application of these nanoparticles.

Gemcitabine, multifunctional nanoparticles, SPION- PLGA drag delivery system, optimized preparation parameters, human breast cancer cell line (MCF-۷)