Back to Search
Start Over
Nanostructured lipid carrier co-delivering tacrolimus and TNF-α siRNA as an innovate approach to psoriasis
- Source :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 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-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
- Subjects :
- Male
medicine.medical_treatment
Down-Regulation
Pharmaceutical Science
02 engineering and technology
Pharmacology
Administration, Cutaneous
030226 pharmacology & pharmacy
Tacrolimus
Mice
03 medical and health sciences
FÁRMACOS IMUNOSSUPRESSORES
Gene therapy
Nanoparticle
0302 clinical medicine
In vivo
Psoriasis
medicine
Animals
Viability assay
Particle Size
RNA, Small Interfering
Psoriasi
Mice, Inbred BALB C
Imiquimod
Tumor Necrosis Factor-alpha
Chemistry
Drug Synergism
021001 nanoscience & nanotechnology
medicine.disease
Controlled release
Topical application
Calcineurin
Disease Models, Animal
Cytokine
Delayed-Action Preparations
Tacrolimu
Liposomes
NIH 3T3 Cells
Nanoparticles
Female
Tumor necrosis factor alpha
0210 nano-technology
Subjects
Details
- ISSN :
- 21903948 and 2190393X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Drug Delivery and Translational Research
- Accession number :
- edsair.doi.dedup.....1d9b6b201fc593c6af0f5d7e05e1eb0c