Study of biodistribution and systemic toxicity of glucose functionalized SPIO/DOX micelles

Abstract

The present study examined the cytotoxicity and magnetic resonance imaging (MRI) distribution of cancer-targeted, MRI-visible polymeric micelles that encapsulate doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) and are conjugated with glucose as a targeting ligand. In this study, the micelles were investigated the clinical potential of glucose-micelles, in vitro cytotoxicity assays of nonencapsulating or SPIO-and-DOX-coencapsulating micelles were performed on L929 mouse fibroblasts, and we found that glucose-micelles did not exert in vitro cytotoxic effects. Next, in vitro MRI detectability of glucose SPIO micelles was evaluated at the loaded SPIO content of 2.5% and 50%, and it was found that glucose-micelles can increase MRI relaxivity (r₂*) at high SPIO loading. Furthermore, 50% SPIO micelles persisted in the blood circulation for up to 5 days (slow liver clearance) as determined by in vivo MRI. For in vivo toxicity evaluation, 50% SPIO/DOX micelles at a dose up to 18 (mg DOX)/(kg body weight) showed no impact on animal health according to clinical chemistry and clinical hematology laboratory testing. Altogether, these results indicate that glucose-micelles can serve as an effective and safe drug delivery system.

Keywords:

• Magnetic resonance imaging (MRI)
• doxorubicin (DOX)
• superparamagnetic iron oxide (SPIO)
• micelles
• cytotoxicity

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research project was supported by Mahidol University, Thailand. The financial support for Nussana Thitichai from the Center of Excellence for Innovation in Chemistry (PERCH-CIC) is gratefully acknowledged.