IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
TOXICITY EVALUATION OF DOXORUBICIN-LOADED MIXED MICELLES ON LARVAE OF ZEBRAFISH
Autor/es:
PRIETO, M. J.; CHIAPPETTA, DIEGO A.; CAGEL, MAXIMILIANO; ALONSO, S. DEL V.; CAGEL, MAXIMILIANO; ALONSO, S. DEL V.; CALIENNI, M. N.; MORETTON, MARCELA A.; MONTANARI, J.; CALIENNI, M. N.; MORETTON, MARCELA A.; MONTANARI, J.; PRIETO, M. J.; CHIAPPETTA, DIEGO A.
Reunión:
Simposio; ICGEB-LAZEN 2018 "V Latin American Zebrafish Network Course and Symposium"; 2018
Institución organizadora:
IBT-UNAM
Resumen:
Background. Doxorubicin hydrochloride is a powerful anthracycline antibiotic used for the treatment of various types of malignancies, particularly ovarian and metastatic breast cancer. However, doxorubicin presents severe side effects, such as hepatotoxicity, brain damage, and cardiotoxicity. We have previously designed doxorubicin-loaded mixed micelles composed of D-α-tocopheryl polyethylene glycol 1000 succinate and Tetronic® T1107, demonstrating an enhanced in vitro antitumoral efficacy versus Doxil® in breast and ovarian human cancer cell lines. Nevertheless, additional studies to assess the potential toxic effects of micellar formulations were needed. Objectives. Determine the potentially toxic and teratogenic effects in vivo of this novel formulation using the zebrafish model. Methods and Results. We studied and compared the effects on zebrafish larvae (between 4 and 7 days post-fecundation) of doxorubicin exposure from different formulations (free doxorubicin, doxorubicin-loaded mixed micelles, and Doxil®). We assessed the effects on the swimming activity, morphological alterations, heart rate, lethality rate and doxorubicin biodistribution. In this work, we observed that the encapsulation of doxorubicin into the mixed micelles reduced the lethal effect, the morphological alterations and the neurotoxic effects of the drug on zebrafish larvae. The three formulations with doxorubicin presented cardiotoxic effects, being the free doxorubicin the one that showed the highest cardiotoxicity and Doxil® the lowest one. On the one hand, it was necessary a 4-fold higher concentration of Doxil® than doxorubicin-loaded mixed micelles to induce an alteration in the heart rate. On the other hand, doxorubicin-loaded mixed micelles were between 4 and 8-fold more cytotoxic in breast and ovarian cancer cell lines than Doxil®. This fact suggests that it may be possible to use lower doses of doxorubicin to achieve the same therapeutic effect and, at the same time, reduce the side effects. Conclusions. This study shows the potential of the doxorubicin-loaded mixed micelles to be an effective doxorubicin-delivery system because it would allow the use lower doses of active principle to achieve the antineoplastic effect, while it could reduce the side effects. Supported by grants from UNQ, CONICET and UBACyT 20020130200038BA.