In vitro and in silico characteristics of doxorubicin-loaded four polymeric-based polysaccharides-modified super paramagnetic iron oxide nanoparticles for cancer chemotherapy and magnetic resonance imaging

Abstract

Super Paramagnetic Iron Oxide Nanoparticles have attracted much attention in drug delivery systems because of their considerable surface-to-volume ratio and content as well. In this regard, in this study, four different formulations of magnetic nanoparticles were synthesized via various polymeric coating layer (beta-cyclodextrin, Chitosan, Gum Arabic, and Alginate) in order to find an appropriate polymer in terms of higher drug loading efficiency and capacity. Molecular dynamics simulation and Quantum mechanics were manipulated to examine the interaction mechanism between the polysaccharide polymers and Doxorubicin. Based on the calculated results, As the best candidate, βCD was chosen for DOX loading. DOX, a hydrophilic drug, was loaded into each of the four formulations. The optimum formulation, Fe₃O₄-ßCD, possessed loading efficiency and capacity, with 97% and 13%, respectively. The selected nanocarrier was fully characterized by Fourier Transform Infrared, VSM, TGA, XRD, SEM, UV-Vis, DLS, and TEM. TEM result exhibited the prepared Fe₃O₄-ßCD-DOX nanoparticles had a spherical shape (core and shell) and the size of around 15 nm. In vitro release investigation was conducted using HPLC analysis in the phosphate-buffered saline in acidic (pH = 5.4) and neutral (pH = 7.4) medium. The obtained results demonstrated that a sustain release performance for more than 72 h with the amount of 50% DOX release in pH = 5.4. Cytotoxicity assay showed the toxicity of bare Fe₃O₄ and Fe₃O₄-ßCDNPsagainst MDA-MB468 cancerous cell and MCF10A normal cell was negligible and DOX-loaded NPs (Fe₃O₄-ßCD-DOX) illustrated a higher toxicity in MDA-MB468 cancerous cells than MCF 10 A normal cells. The results showed that Fe₃O₄-ßCD-DOXNPs could improve the therapeutic efficacy and also reduce the adversarial effects; accordingly, the prepared system could be served as a promising drug delivery system in cancer treatment.

Graphical Abstract

Keywords:

• β-cyclodextrin
• doxorubicin
• magnetic nanoparticles
• molecular dynamics simulation
• quantum mechanics

Acknowledgments

The authors would like to thank the Vice Chancellor for Research of Zanjan University of Medical Sciences (grant no. A-12-1077-13, ethical code: IR.ZUMS.REC.1398.091). Authors also like to acknowledge the cooperation of Tehran University of Medical Sciences for Research Laboratory. This article is a part of a thesis (No. A-12-1077-13) submitted for PhD degree in Faculty of Pharmacy, Zanjan University of Medical Sciences.