Zebrafish ( Danio rerio ) model as an early stage screening tool to study the biodistribution and toxicity profile of doxorubicin-loaded mixed micelles

CALIENNI, MARÍA NATALIA; CAGEL, MAXIMILIANO; MONTANARI, JORGE; MORETTON, MARCELA A.; PRIETO, MARIA JIMENA; CHIAPPETTA, DIEGO A.; DEL VALLE ALONSO, SILVIA

TOXICOLOGY AND APPLIED PHARMACOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2018

0041-008X

Doxorubicin (DOX) hydrochloride is a powerful anthracycline antibiotic used forthe treatment of various types of malignancies, particularly ovarian andmetastatic breast cancer. However, DOX presents severe side effects, such ashepatotoxicity, nephrotoxicity, dose-limiting myelosuppression, brain damageand cardiotoxicity. A liposomal formulation, Doxil®, was approved by the FDA,which has managed to reduce the number of cardiac events in patients withmetastatic breast cancer. However, in comparison to free DOX, Doxil® has notshown significant improvements regarding survival. We have previouslydesigned DOX-loaded mixed micelles (MMDOX) composed of D-α-tocopherylpolyethylene glycol 1000 succinate (TPGS) and Tetronic® T1107. To assess thepotential toxic effects of this novel formulation, in this work the zebrafish (Daniorerio) model was used to evaluate its in vivo toxicity and teratogenicity. Thisstudy evaluated and compared the effects of DOX exposure from differentformulations (free DOX, MMDOX and Doxil®) on the swimming activity,morphological alterations, cardiac rhythm, lethality rate and DOX biodistribution.MMDOX showed lower lethal effects, morphological alterations and neurotoxiceffects than the free drug. This study shows the potential of the MMDOX to bean effective DOX-delivery system because it could reduce the side effects.