Nanostructured lipid carrier co-delivering tacrolimus and TNF-alpha siRNA as an innovate approach to psoriasis

Autor(es)

Viegas, Juliana Santos Rosa ; Praca, Fabiola Garcia ; Caron, Angelo Luis ; Suzuki, Isabella ; Silvestrini, Ana Vitoria Pupo ; Medina, Wanessa Silva Garcia ; Del Ciampo, Jose Orestes ; Kravicz, Marcelo ; Bentley, Maria Vitoria Lopes Badra

• Tipo de documento: Artigo Científico
• Fonte: DRUG DELIVERY AND TRANSLATIONAL RESEARCH; v. 10, n. 3, p. 15-pg., 2020-02-14.

Resumo

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-alpha. 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-alpha expression about 7-fold and presenting a synergic effect between the TAC and TNF-alpha 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. Graphical abstract (AU)

• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático