In Vivo Toxicity Studies of Chitosan-Coated Cobalt Ferrite Nanocomplex for Its Application as MRI Contrast Dye

ACS Appl Bio Mater. 2020 Nov 16;3(11):7952-7964. doi: 10.1021/acsabm.0c01069. Epub 2020 Oct 27.

Abstract

Cobalt ferrite nanoparticle (CFN) has received attention in magnetic resonance imaging (MRI) as a promising contrast agent due to its higher saturation magnetization and magneto-crystalline anisotropy. However, the in vitro cytotoxicity of CFN has raised concern for its biomedical application as a diagnostic agent. The coating of CFN by a biocompatible polymer such as chitosan (CH) might lessen the biocompatibility concern. Therefore, in this study, we examined the applicability of chitosan-coated cobalt ferrite nanoparticle (CCN) as an MRI contrast dye and investigated its biocompatibility in vivo. Phantom MRI images revealed that the relaxivity of CCN was 121 (±8) mM-1s-1, indicating the potential of CCN as a T2-weighted contrast agent. A single intravenous (iv) administration of CCN (10 mg/kg) improved the contrast of magnetic-resonance-imaging-based angiography (MRA) and brain-MRI in male albino Wistar rats compared to the control. Furthermore, toxicity studies dependent on dose (1-20 mg/kg) and time (1-28 days) in male albino Wistar rats confirmed the in vivo biocompatibility of CCN. The physical, hematological, biochemical, and histopathological observation assured that a single iv injection of CCN up to 20 mg/kg was well adjusted with liver, kidney, heart, and brain functions. The findings of the current study consolidate CCN as a promising candidate for MRI contrast dye.

Keywords: MRI contrast; chitosan; chitosan-coated cobalt ferrite; cobalt ferrite; in vivo toxicity and biocompatibility; relaxivity.