Since psoriasis is an immuno-mediated skin disease, long-term therapies are necessary for its treatment. In clinical investigations, tacrolimus (TAC), a macrolide immunosuppressive inhibitor of calcineurin, arises as an alternative for the treatment of psoriasis, acting in some cytokines involved in the pathogenesis of the disease. Here, we aim to study the psoriasis treatment with TAC and siRNA for one of most cytokines expressed in psoriasis, the TNF-α. A multifunctional nanostructure lipid carrier (NLC) was developed to co-delivery TAC and siRNA. Results showed that the particle size and zeta potential were around 230 nm and + 10 mV, respectively. The release study demonstrated a controlled release of TAC, and the permeation and retention profile in the skin tissue show to be promising for topical application. The cell viability and uptake in murine fibroblast presented low toxicity associated to uptake of NLC in 4 h, and finally, the in vivo animal model demonstrates the efficiency of the NLC multifunctional, exhibiting a reduction of the cytokine TNF-α expression about 7-fold and presenting a synergic effect between the TAC and TNF-α siRNA. The developed system was successfully to treat in vivo psoriatic animal model induced by imiquimod and the synergic combination was reported here for the first time.
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This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and the National Institute of Science and Technology in Pharmaceutical Nanotechnology, a transdisciplinary approach INCT-NANOFARMA, which is supported by São Paulo Research Foundation (FAPESP, Brazil) grant #2014/50928-2 and by “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq, Brazil) grant #465687/2014-8.
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The authors declare that they have no conflict of interest.
Consent for animal studies
The protocol of in vivo animal studies (the “In vivo studies” section) is in accordance with the National Animal Experiment Control Board and is registered under the number 18.1.385.60.2 by the School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Brazil.
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Viegas, J.S.R., Praça, F.G., Caron, A.L. et al. Nanostructured lipid carrier co-delivering tacrolimus and TNF-α siRNA as an innovate approach to psoriasis. Drug Deliv. and Transl. Res. (2020). https://doi.org/10.1007/s13346-020-00723-6
- Topical application
- Gene therapy