Delivery of epirubicin via slow infusion as a strategy to mitigate chemotherapy-induced cardiotoxicity

Figures

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  Fig 1. Pharmacokinetic profiles of intraperitoneal bolus injection and intraperitoneal micro osmotic pump infusion in rats. (A) Schematic representation of the experimental design and timing of sample collection. (B) The mean plasma concentrations of the bolus group (solid black circle) and those of the pump infusion group (open circle) are as labeled. The error bars represent the 95% confidence intervals.

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  Fig 2. Histopathology of epirubicin-induced myocardial damage. Representative photomicrographs of hematoxylin-eosin-stained slides of rat heart tissues from 3 groups of mice [control, epirubicin (bolus), and epirubicin (infusion)] are shown as labeled. Features such as focal interstitial hemorrhage (blue arrow), eosinophilic enhancement (solid black arrow), and wavy myocardial fibers (yellow arrow head) are indicated. Due to heart beats, paralyzed myocardial fibers become wavy, and this is a sign of loss of contractility.

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  Fig 3. Differential impact of two epirubicin administration methods on biomarkers of myocardial damage and complete blood counts. The IP bolus group is represented by solid black dots, and the micro osmotic pump group by white dots. The horizontal axis is the time since completing epirubicin administration in hours. Error bars represent standard error of the mean.

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  Fig 4. The log dose-response curve of the 4T1-luc cell line to epirubicin. The protein biomass relative to control was measured by the sulforhodamine B assay. A sigmoidal curve was fitted to the data. Error bars represent 95% confidence intervals.

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  Fig 5. Equal in vivo antineoplastic efficacy of two methods of epirubicin administration. (A) Schematic representation of the experimental design and timing of data and sample collection from mice. (B) The tumor growth curves of orthotopic breast cancer allografts are shown for the three different groups of mice as labeled. Error bars represent standard errors; **, P<0.01; ***, P<0.001. (C) The photonic radiance from tumors was measured by bioluminescence imaging at 10 min post injection of D-luciferin. The error bars represent standard errors; *, P<0.05; **, P<0.01. (D) A representative comparison of bioluminescence intensity at 10 min in the three labeled groups of mice is shown. The color scale of the photon counts is labeled to the left of the images.