Doxorubicin Loaded Dextran-coated Superparamagnetic Iron Oxide Nanoparticles with Sustained Release Property: Intracellular Uptake, Pharmacokinetics and Biodistribution Study

Background: Due to the short biological half-life and serious side effects (especially for heart and kidney), the application of Doxorubicin (Dox) in clinical therapy is strictly limited. To overcome these shortcomings, a novel sustained release formulation of doxorubicin loaded dextran-coated superparamagnetic iron oxide nanoparticles (Dox-DSPIONs) was prepared. Objectives: The purpose of this study was to evaluate the intracellular uptake behavior of Dox-DSPIONs, and to investigate its pharmacokinetics and biodistribution properties. Method: Confocal laser scanning microscopy was employed to study the intracellular uptake and release properties of Dox from Dox-DSPIONs in SMMC-7721 cells. A simple high performance liquid chromatography with fluorescence detection (HPLC-FLD) method was established to study the pharmacokinetics and biodistribution of Dox-DSPIONs in vivo after intravenous administration, and compared with free Dox. Results: Intracellular uptake experiment indicated that Dox could be released sustainedly from Dox-DSPIONs over time. The pharmacokinetics parameters displayed that the T-1/2 and AUC(0-24h) of Dox-DSPIONs were higher than those of free Dox, while the C-max of Dox-DSPIONs was significantly lower than that of free drug. The biodistribution behaviors of the drug were altered by Dox-DSPIONs in mice, which showed obvious liver targeting, and significantly reduced the distribution of the drug in the heart and kidney. Conclusion: Dox-DSPIONs has the sustained release property in vitro and in vivo, which could significantly prolong blood circulation time, improve bioavailability and reduce the side effects of Dox. Therefore, the novel formulation of Dox-DSPIONs has the potential as a promising drug delivery system in cancer therapy.