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Anti-HPV Nanoemulsified-Imiquimod: A New and Potent Formulation to Treat Cervical Cancer

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Abstract

Cervical cancer is associated with the human papilloma virus (HPV) and nowadays is the fourth most frequent cancer among women. One of the treatments for this disease is based on the application of imiquimod. In this study, we postulated that the use of imiquimod in nanoemulsion results in a better antitumoral effect than the drug administered in its nonencapsulated form for the treatment of cervical cancer. Permeability studies using vaginal mucosa, as membrane, and in vitro studies involving cervical cancer cells (viability, clonogenic assay, and cell death analysis) were performed. We showed that low amount of encapsulated imiquimod permeated the vaginal mucosa. However, a higher percentage of cells died after the treatment with low amount (3.0 μmol L−1) of the formulation compared to the free drug. In addition, the innovative formulation presented a combinatory mechanism of cell death involving autophagy and apoptosis. Our results demonstrate that the imiquimod-loaded nanoemulsioncan be an alternative product for the treatment of cervical cancer validating the hypothesis.

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Funding

The authors thank the financial support of the following Brazilian agencies: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); INCT-NANOFARMA (FAPESP, Brazil) Grant #2014/50928-2 and INCT-NANOFARMA (CNPq, Brazil) Grant # 465687/2014-8; PRONEX FAPERGS/CNPq 12/2014 – Grant 16/2551-0000467-6; and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Post-Doc scholarship to the author P.A.M, Procad-CAPES, Edital n 071/2013-15819; CNPq Grants to A.R.P. ad S.S.G.).

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Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil

    Luiza Abrahão Frank, P. Chaves, R. C. R. Beck, A. Buffon, A. R. Pohlmann & Silvia S. Guterres

  2. Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752/405, Porto Alegre, RS, CEP 90610-000, Brazil

    Luiza Abrahão Frank, R. P. Gazzi, F. Peña & Silvia S. Guterres

  3. Laboratorio de Biologia Celular, Universidade Federal de Ciências da Saude de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

    P. A. Mello & A. R. Pohlmann

  4. Laboratorio de Análises Bioquímicas e Citológicas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

    P. A. Mello

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  1. Luiza Abrahão Frank
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  2. R. P. Gazzi
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Correspondence to Luiza Abrahão Frank or Silvia S. Guterres.

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Frank, L.A., Gazzi, R.P., Mello, P.A. et al. Anti-HPV Nanoemulsified-Imiquimod: A New and Potent Formulation to Treat Cervical Cancer. AAPS PharmSciTech 21, 54 (2020). https://doi.org/10.1208/s12249-019-1558-x

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