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Mixed micellar system for codelivery of doxorubicin and caffeic acid phenethyl ester: design and enhanced antitumor activity

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Abstract

Multifunctional nanocarriers of two or more anticancer drugs with different pharmacological mechanisms are being developed for combination therapy, which aims at achieving synergistic effects in cancer treatment and overcoming the increasingly common problem of drug resistance. This contribution reports the fabrication of functional nanosized micellar carriers of doxorubicin (DOX) and caffeic acid phenethyl ester (CAPE) via coassembly of two well-defined amphiphilic ABA triblock copolymers comprising identical hydrophobic poly(ε-caprolactone) (PCL) blocks and different hydrophilic segments – poly(ethylene oxide) (PEO) or poly(acrylic acid) (PAA). CAPE was embedded into the PCL core via hydrophobic interactions, while DOX was loaded within a mixed PAA/PEO corona layer through complexation. The main physico-chemical properties of blank and dual drug-loaded micelles were investigated using dynamic and electrophoretic light scattering and transmission electron microscopy. Loading of CAPE and DOX increased the size and size distribution of carriers to some extent. However, the mixed micellar system was characterized by good colloidal stability and sustained release of the two drugs. The cytotoxic effect of DOX/CAPE-loaded mixed micelles in drug-resistant lymphoma cells expressing the multidrug resistance (MDR1) gene (L5178Y MDR1) was assessed.

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Acknowledgements

This work was supported by the Bulgarian National Science Fund (Grant DN 09/1-2016). The authors are grateful to Professor V. Bankova for providing CAPE.

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Authors and Affiliations

  1. Institute of Polymers, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria

    Katya Kamenova, Georgy Grancharov & Petar D. Petrov

  2. Faculty of Pharmacy, Medical University of Sofia, 1000, Sofia, Bulgaria

    Borislav Tzankov, Denitsa Aluani, Virginia Tzankova & Krassimira Yoncheva

  3. Faculty of Pharmacy, Medical University of Pleven, 5800, Pleven, Bulgaria

    Stanislav Tzankov

Authors
  1. Katya Kamenova
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  2. Georgy Grancharov
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  3. Borislav Tzankov
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  4. Denitsa Aluani
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  5. Virginia Tzankova
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  6. Stanislav Tzankov
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  7. Krassimira Yoncheva
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  8. Petar D. Petrov
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Correspondence to Petar D. Petrov.

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Kamenova, K., Grancharov, G., Tzankov, B. et al. Mixed micellar system for codelivery of doxorubicin and caffeic acid phenethyl ester: design and enhanced antitumor activity. Polym J 53, 471–479 (2021). https://doi.org/10.1038/s41428-020-00442-2

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