Double-Loaded Doxorubicin/Resveratrol Polymeric Micelles Providing Low Toxicity on Cardiac Cells and Enhanced Cytotoxicity on Lymphoma Cells

Figures

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  Figure 1. Encapsulation efficiency (EE) and loading degree (LD) in the double-loaded micelles (a) and Flory–Huggins parameter calculated for doxorubicin (Dox) and resveratrol (Res) with respect to PPO block (b).

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  Figure 2. Structures and partition coefficients of resveratrol (a) and doxorubicin (b) and schematic presentation of their loading in the micelles (c).

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  Figure 3. Transmission electron microscopy of empty (a) and doxorubicin/resveratrol-loaded micelles (b).

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  Figure 4. Mean diameters (a) and digital image (b) of empty (EM) and double-loaded doxorubicin/resveratrol micelles (DRM).

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  Figure 5. FTIR spectra of doxorubicin (Dox), resveratrol (Res), empty (EM) and double-loaded micelles (DRM).

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  Figure 6. Powder XRD patterns of Pluronic F127 (F127), empty micelles (EM), resveratrol (Res), doxorubicin (Dox), single resveratrol-loaded micelles (RM), single doxorubicin-loaded micelles (DM) and the double-loaded micelles (DRM).

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  Figure 7. In vitro release profiles of doxorubicin and resveratrol from the double-loaded micelles in buffers with pH = 5 (a) and pH = 7.4 (b).

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  Figure 8. In vitro cytotoxic effect of pure doxorubicin in H9c2 cells after 24 h treatment.

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  Figure 9. In vitro cell viability of cardioblasts (H9c2) after treatment with the double-loaded doxorubicin/resveratrol micelles (DRM) and referent hydroalcoholic solutions of both drugs (DR). Ctrl—non-treated cells; DRM1 (double-loaded micelles) and DR1 (standard solution) containing 0.25 µM Dox and 1.3 µM Res (a); DRM2 (double-loaded micelles) and DR2 (standard solution) containing 0.25 µM Dox and 0.3 µM Res (a); DRM3 (double-loaded micelles) and DR3 (standard solution) containing 5 µM Dox and 26 µM Res (b); DRM4 (double-loaded micelles) and DR4 (standard solution) containing 5 µM Dox and 6 µM Res (b); * p < 0.05; ** p < 0.01; *** p < 0.001 vs. doxorubicin group.

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  Figure 10. In vitro cytotoxic effect in lymphoma L5178 cells treated with the double-loaded doxorubicin/resveratrol micelles (DRM) and corresponding hydroalcoholic solutions of doxorubicin/resveratrol (DR). Ctrl—non-treated cells; DRM1 (double-loaded micelles) and DR1 (standard solution) containing 0.25 µM Dox and 1.3 µM Res (a); DRM2 (double-loaded micelles) and DR2 (standard solution) containing 0.25 µM Dox and 0.3 µM Res (a); DRM3 (double-loaded micelles) and DR3 (standard solution) containing 5 µM Dox and 26 µM Res (b); DRM4 (double-loaded micelles) and DR4 (standard solution) containing 5 µM Dox and 6 µM Res (b); * p < 0.05; ** p < 0.01; *** p < 0.001 vs. doxorubicin group; # p < 0.05; ### p < 0.001 for double-loaded micelles vs. hydroalcoholic solutions.