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

Abstract

Doxorubicin (DOX) hydrochloride is a powerful anthracycline antibiotic used for the treatment of various types of malignancies, particularly ovarian and metastatic breast cancer. However, DOX presents severe side effects, such as hepatotoxicity, nephrotoxicity, dose-limiting myelosuppression, brain damage and cardiotoxicity. A liposomal formulation, Doxil®, was approved by the FDA, which has managed to reduce the number of cardiac events in patients with metastatic breast cancer. However, in comparison to free DOX, Doxil® has not shown significant improvements regarding survival. We have previously designed DOX-loaded mixed micelles (MMDOX) composed of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and Tetronic® T1107. To assess the potential toxic effects of this novel formulation, in this work the zebrafish (Danio rerio) model was used to evaluate its in vivo toxicity and teratogenicity. This study evaluated and compared the effects of DOX exposure from different formulations (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 neurotoxic effects than the free drug. This study shows the potential of the MMDOX to be an effective DOX-delivery system because it could reduce the side effects.

The past, present, and future of breast cancer models for nanomedicine development

“…Zebrafish models may also find use in determining parameters including lethal dose, acute toxicity, teratogenicity, and organ-specific toxicity, which all represent established applications [237] . For example, Calienni et al employed zebrafish to compare the in vivo toxicity and teratogenicity of doxorubicin-loaded mixed micelles (MMDOX) composed of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and Tetronic® T1107 with free doxorubicin and Doxil® [238] . MMDOX displayed lower levels of lethality, morphological alterations, and neurotoxic effects compared to free doxorubicin; however, but Doxil® performed better overall.…”

“… 3D: MCF7 and MDA-MB-231 in low attachment plates. Cell toxicity, CSC-resistance assay, cell transformation assay MCF7 and MDA-MB-231 orthotopically injected in NOD-SCID mice Antitumor efficacy, biodistribution, safety [169] Doxorubicin-loaded mixed micelles composed of TPGS and Tetronic® T1107 – – Wild-type adult zebrafish Biodistribution, safety [238] Polymer Conjugates PEG‐pLA‐pTBPC-Dox 2D: MDA‐MB‐231, MCF7, HCC70, MDA‐MB‐468, MCF‐10A. 3D: MDA‐MB‐231 spheroids hanging drop method.…”

BSA-capped gold nanoclusters as potential theragnostic for skin diseases: Photoactivation, skin penetration, in vitro, and in vivo toxicity

“…The potential of GNC as photosensitizers and singlet oxygen production has been recognized [21][22][23], but very few works have studied the production of singlet oxygen by BSA-capped GNC [24], while there are no records of skin penetration studies out of a work on simulation [25], which predicts a big increment in permeability when gold nanoparticles range smaller than 2 nm, i.e., the upper size limit of GNC. In need for in vivo testing, Zebrafish (Danio rerio) is a versatile intermediate model, useful for toxicity evaluation of nanomaterials in general [26,27].…”

Lecithin-Based Dermal Drug Delivery for Anti-Pigmentation Maize Ceramide

“…Recent studies demonstrated a close correlation between zebrafish and human pigmentation [9][10][11], with many depigmenting agents identified using zebrafish embryos or larvae [12][13][14][15]. In addition, zebrafish are now used to test several types of drug delivery systems, including liposomes [16,17], micelles [18], and nanoparticles [19][20][21][22].…”