Comparative In Vitro Toxicity Study of Docetaxel and Nanoxel, a Docetaxel-Loaded Micellar Formulation Using Cultured and Blood Cells

Abstract

Nanoxel-PM TM (Nanoxel) is a docetaxel-loaded methoxy-poly(ethylene glycol)- block -poly(D,L-lactide) (mPEG-PDLLA). 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 Ca 2+ and 5-hydroxytryptamine-evoked Ca 2+ 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.

Green Synthesis of Silver Nanoparticles by Cytobacillus firmus Isolated from the Stem Bark of Terminalia arjuna and Their Antimicrobial Activity

“…The absorbance of the supernatant was measured against blank at 415 nm for hemoglobin leakage (Beckman coulter DU-730, Brea, CA, USA). Untreated erythrocytes lysed in distilled water represent 100% hemolysis [ 22 ].…”

“…Erythrocytes (5% hematocrit) in Ringer solution ((in mM) 125 NaCl, 5 KCl, 1 MgSO 4 , 32 N-2hydroxyethylpiperazine-N-2-ethane sulfonic acids (HEPES), 5 glucose, 1 CaCl 2, pH 7.4)) were incubated independently with indicated concentrations of diluted AgNPs (0.5, 1, 1.5, 2, and 2.5 µg/µL) with 1× PBS followed by incubation for 6 h at 37 • C. The absorbance of the supernatant was measured against blank at 415 nm for hemoglobin leakage (Beckman coulter DU-730, Brea, CA, USA). Untreated erythrocytes lysed in distilled water represent 100% hemolysis [22].…”

Autophagy-mediated occludin degradation contributes to blood–brain barrier disruption during ischemia in bEnd.3 brain endothelial cells and rat ischemic stroke models

“…bEnd.3 cells were seeded on 48-or 96-well plates and incubated to confluence. To determine the effect of OGD on cell viability, cells were exposed to OGD for 18 h and then incubated with 0.5 mg/mL MTT for 2 h [21]. The supernatants were discarded and insoluble formazan was dissolved using dimethyl sulfoxide.…”

Methylglyoxal-Induced Dysfunction in Brain Endothelial Cells via the Suppression of Akt/HIF-1α Pathway and Activation of Mitophagy Associated with Increased Reactive Oxygen Species

“…After 10 min of incubation, the fluorescence of PI was measured using an excitation and emission wavelength of 493 and 632 nm, respectively, in EnSpire multimode spectrophotometer (PerkinElmer, Santa Clara, CA, USA). To evaluate the MTT reduction potential of bEnd.3 cells after MG exposure, we added 0.5 mg/mL MTT at the end of the stimulus exposure [25]. After 2 h of incubation, formazan was dissolved in dimethyl sulfoxide.…”