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Anti-tumoral effect of doxorubicin-loaded poly(vinyl alcohol)/poly(vinyl acetate) microspheres in a rat model

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Abstract

Porous and degradable poly(vinyl alcohol)/poly(vinyl acetate) microspheres (PVA/PVAc-Ms) were synthesized with a diameter in the range of 20–55 μm by suspension polymerization method suitable for loading and releasing doxorubicin (DOX). In addition, the biological efficacy in vitro of PVA/PVAc-Ms and their anti-tumoral effect in vivo in a rat model were evaluated. The size distribution and morphology of PVA/PVAc-Ms were assessed by microscopy. In vitro degradability was tested according to ISO 10993-13. DOX loading and DOX release were quantified by a multi-mode reader. The biological efficacy in vitro was assessed by cell viability quantification. The anti-tumoral effect in vivo was assessed in a subcutaneous tumor model in rats that received an intra-tumoral injection of PVA/PVAc-Ms: empty Ms in group 1 (n = 16) or DOX (2000 μg/mL)-loaded Ms in group 2 (n = 16). The mean tumor volume was calculated and samples were processed for histopathological analysis. PVA/PVAc-Ms exhibited a porous surface, a spherical morphology and a diameter in the range of 20–55 μm. The in vitro degradability was 30% in 38 days. From DOX concentrations of 333 and 2000 μg/mL, Ms loaded 40% and 21% and released 1.5% and 0.6%, respectively. Cell viability was reduced with DOX loaded PVA/PVAc-Ms. The mean tumor volume was 167.7 ± 77.6 mm3 in group 1 and 96.2 ± 58.2 mm3 in group 2 (P = 0.0061). The mean percentage value of necrotic areas was 37% in group 1 and 45% in group 2 (no significancy). In conclusion, porous PVA/PVAc-Ms synthesized can load and release DOX, reduce cell viability in vitro and produce an anti-tumoral effect in vivo.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable requests.

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Acknowledgements

The authors gratefully acknowledge Bernardo Pentke and Ivana Tapia for the technical support, Lucas Colombo for cells culture, Silvia Vanzulli for histopathological analysis, and Andrés Vidal for animal care.

Author information

Authors and Affiliations

  1. Nuclear Materials Department, National Atomic Energy Commission (CNEA), San Carlos de Bariloche, Argentina

    Luisa Ambrosio & Miguel O. Prado

  2. National Atomic Energy Commission (CNEA), Ezeiza, Argentina

    Luciano Parodi

  3. National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Argentina

    Luisa Ambrosio & Miguel O. Prado

  4. University of Buenos Aires (UBA), Ciudad Autónoma de Buenos Aires, Argentina

    Luisa Ambrosio & Jorge Cardoso Cúneo

  5. Nuclear Medicine Center, Institute of Oncology Angel H. Roffo (COMNIR), University of Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina

    Luisa Ambrosio, Clara Sanchez Terrero, Ana Cristina Zarlenga & Jorge Cardoso Cúneo

  6. Department of Digestive Surgery, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina

    Jorge Cardoso Cúneo

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  1. Luisa Ambrosio
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  2. Clara Sanchez Terrero
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  3. Miguel O. Prado
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  4. Luciano Parodi
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  6. Jorge Cardoso Cúneo
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by LA, and CST. All authors read and approved the final manuscript.

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Correspondence to Jorge Cardoso Cúneo.

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The experiments were approved by CNEA Institutional Animal Care Commission and were conducted according to European Community and American rules of animal care and use guidelines.

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Ambrosio, L., Sanchez Terrero, C., Prado, M.O. et al. Anti-tumoral effect of doxorubicin-loaded poly(vinyl alcohol)/poly(vinyl acetate) microspheres in a rat model. Iran Polym J 32, 287–297 (2023). https://doi.org/10.1007/s13726-022-01121-0

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