Comparative In Vitro Toxicity Study of Docetaxel and Nanoxel, a Docetaxel-Loaded Micellar Formulation Using Cultured and Blood Cells
Toxicol. Res. 2019;35:201−207
Published online April 15, 2019;  https://doi.org/10.5487/TR.2019.35.2.201
© 2019 Korean Society of Toxicology.

Van Quan Do, Kwang-Hoon Park, Jung-Min Park and Moo-Yeol Lee

College of Pharmacy, Dongguk University, Goyang, Korea
Moo-Yeol Lee, College of Pharmacy, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Korea
E-mail: mlee@dongguk.edu
Received: August 29, 2018; Revised: September 18, 2018; Accepted: October 4, 2018
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Nanoxel-PMTM (Nanoxel) is a docetaxel-loaded methoxy-poly(ethylene glycol)-block-poly(D,L-lactide) (mPEGPDLLA). This newly developed and marketed nanoformulation exhibits an improved pharmacokinetic profile, efficacy, and safety. Although the safety of Nanoxel to docetaxel as well as its bioequivalence must be clinically confirmed, all biological activities have not been examined in in vitro or in vivo studies. Here, the toxicity in a cultured cell system and the effects on blood cells were tested with Nanoxel and docetaxel. The in vitro cytotoxicity of Nanoxel was found to be comparable to or slightly lower than that of docetaxel depending on the concentrations tested or the cell types. Neither docetaxel nor Nanoxel induced erythrocytes hemolysis and produced reactive oxygen species up to 100 μM. However, Nanoxel was able to enhance the aggregatory response of platelets to collagen, whereas docetaxel attenuated such aggregation in a range of 50-100 μM, while thrombin-induced aggregation was not affected by either of them. Docetaxel or Nanoxel did not alter basal level of Ca2+ and 5-hydroxytryptamine-evoked Ca2+ transient in vascular smooth muscle cells. These results suggest that the mPEG-PDLLA micellar formulation alters the toxicological properties of docetaxel, and that extra cautions are needed when evaluating the safety of nanomedicine.
Keywords : Docetaxel, Nanoxel, Nanomedicine, Cytotoxicity, Platelet aggregation


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