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Nanostructured lipid carrier co-delivering tacrolimus and TNF-α siRNA as an innovate approach to psoriasis.
- Source :
-
Drug delivery and translational research [Drug Deliv Transl Res] 2020 Jun; Vol. 10 (3), pp. 646-660. - Publication Year :
- 2020
-
Abstract
- 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. Graphical abstract.
- Subjects :
- Administration, Cutaneous
Animals
Delayed-Action Preparations
Disease Models, Animal
Down-Regulation
Drug Synergism
Female
Liposomes
Male
Mice
Mice, Inbred BALB C
NIH 3T3 Cells
Nanoparticles
Particle Size
Psoriasis chemically induced
Psoriasis genetics
RNA, Small Interfering pharmacology
Tacrolimus pharmacology
Tumor Necrosis Factor-alpha antagonists & inhibitors
Imiquimod adverse effects
Psoriasis drug therapy
RNA, Small Interfering administration & dosage
Tacrolimus administration & dosage
Tumor Necrosis Factor-alpha genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2190-3948
- Volume :
- 10
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Drug delivery and translational research
- Publication Type :
- Academic Journal
- Accession number :
- 32060883
- Full Text :
- https://doi.org/10.1007/s13346-020-00723-6