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Development and Evaluation of Sustained-Release Etoposide-Loaded Poly(ε-Caprolactone) Implants

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Abstract

Poly(ε-caprolactone) implants containing etoposide, an important chemotherapeutic agent and topoisomerase II inhibitor, were fabricated by a melt method and characterized in terms of content uniformity, morphology, drug physical state, and sterility. In vitro and in vivo drug release from the implants was also evaluated. The cytotoxic activity of implants against HeLa cells was studied. The short-term tolerance of the implants was investigated after subcutaneous implantation in mice. The original chemical structure of etoposide was preserved after incorporation into the polymeric matrix, in which the drug was dispersed uniformly. Etoposide was present in crystalline form in the polymeric implant. In vitro release study showed prolonged and controlled release of etoposide, which showed cytotoxicity activity against HeLa cells. After implantation, good correlation between in vitro and in vivo drug release was found. The implants demonstrated good short-term tolerance in mice. These results tend to show that etoposide-loaded implants could be potentially applied as a local etoposide delivery system.

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ACKNOWLEDGMENTS

The authors would like to thank Quiral Química do Brasil S.A. for etoposide donation and CNPq, FAPEMIG, and Brazilian Pharmacopoeia for the financial support.

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Authors and Affiliations

  1. Department of Pharmaceuticals Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Ana Gabriela Reis Solano, Armando da Silva Cunha Jr & Gérson Antônio Pianetti

  2. Faculty of Pharmacy, Federal University of São João Del Rei, Divinópolis, Minas Gerais, Brazil

    Ana Gabriela Reis Solano, Adriana de Fátima Pereira, Flavia Carmo Horta Pinto, Letícia Gonçalves Resende Ferreira, Leandro Augusto de Oliveira Barbosa & Gisele Rodrigues da Silva

  3. Ezequiel Dias Foundation, Belo Horizonte, Minas Gerais, Brazil

    Silvia Ligório Fialho

  4. Federal Center of Technological Education, Belo Horizonte, Minas Gerais, Brazil

    Patrícia Santiago de Oliveira Patricio

  5. Rua Sebastião Gonçalves Coelho, 400, Bloco B, sala 301, Chanadour, 35501-296, Divinópolis, Minas Gerais, Brazil

    Ana Gabriela Reis Solano

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  1. Ana Gabriela Reis Solano
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  2. Adriana de Fátima Pereira
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Correspondence to Ana Gabriela Reis Solano.

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Solano, A.G.R., de Fátima Pereira, A., Pinto, F.C.H. et al. Development and Evaluation of Sustained-Release Etoposide-Loaded Poly(ε-Caprolactone) Implants. AAPS PharmSciTech 14, 890–900 (2013). https://doi.org/10.1208/s12249-013-9977-6

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