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Hydrogel Containing Silibinin-Loaded Pomegranate Oil-Based Nanocapsules for Cutaneous Application: In Vitro Safety Investigation and Human Skin Biometry and Permeation Studies

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Abstract

In previous studies, we developed a hydrogel formulation containing silibinin-loaded pomegranate oil nanocapsules (HG-NCSB) that had improved in vivo anti-inflammatory action in comparison to non-encapsulated silibinin. To determine skin safety and whether the nanoencapsulation influences silibinin skin permeation, NCSB skin cytotoxicity, HG-NCSB permeation in human skin, and a biometric study with healthy volunteers were conducted. The formulation of nanocapsules was prepared by the preformed polymer method while the HG-NCSB was obtained by thickening the suspension of nanocarriers with gellan gum. The cytotoxicity and phototoxicity of nanocapsules were assessed in Keratinocytes (HaCaT) and fibroblast (HFF-1) using the MTT assay. The hydrogels were characterized regarding the rheological, occlusive, and bioadhesive properties, and silibinin permeation profile in human skin. The clinical safety of HG-NCSB was determined by cutaneous biometry in healthy human volunteers. NCSB yielded better cytotoxicity results than the blank nanocapsules (NCPO). NCSB did not cause photocytotoxicity, while NCPO and the non-encapsulated substances (SB and pomegranate oil) were phototoxic. The semisolids presented non-Newtonian pseudoplastic flow, adequate bioadhesiveness, and low occlusive potential. The skin permeation demonstrated that HG-NCSB retained a higher SB amount in the outermost layers than HG-SB. In addition, HG-SB reached the receptor medium and had a superior concentration of SB in the dermis layer. In the biometry assay, there was no significant cutaneous alteration after the administration of any of the HGs. Nanoencapsulation promoted greater SB retention in the skin, averted percutaneous absorption, and made the topical use of SB and pomegranate oil safer.

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Funding

This research was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-BR) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-BR) for the financial support (456863/2014-1).

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Authors and Affiliations

  1. Laboratório de Tecnologia Farmacêutica, Programa de Pós-graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, 97105-900, Brazil

    Marila C. L. Marchiori, Cristina Rigon, Fernanda da S. Jardim, Laura M. Giuliani & Letícia Cruz

  2. Curso de Biomedicina, Centro Universitário Franciscano, Santa Maria, Brazil

    Priscila M. Copetti, Michele R. Sagrillo & Aline F. Ourique

Authors
  1. Marila C. L. Marchiori
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  2. Cristina Rigon
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  3. Fernanda da S. Jardim
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  4. Laura M. Giuliani
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  5. Priscila M. Copetti
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  6. Michele R. Sagrillo
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  7. Aline F. Ourique
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  8. Letícia Cruz
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Contributions

This study was conceptualized and designed by Marchiori, M. C. L., Rigon, C., Giuliani, L. M., and Cruz, L. The experiments and data analyses were performed by Marchiori, M. C. L., Rigon, C., Giuliani, L. M., Copetti, P. M., Sagrillo, M. R., Ourique, A. F. The manuscript was written by Marchiori, M. C. L., and edited by Cruz, L., Sagrillo, M. R., and Ourique, A. F. All authors reviewed the manuscript and approved the final version.

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Correspondence to Letícia Cruz.

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Marchiori, M.C.L., Rigon, C., da S. Jardim, F. et al. Hydrogel Containing Silibinin-Loaded Pomegranate Oil-Based Nanocapsules for Cutaneous Application: In Vitro Safety Investigation and Human Skin Biometry and Permeation Studies. AAPS PharmSciTech 24, 138 (2023). https://doi.org/10.1208/s12249-023-02606-8

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