Psoriasis is a chronic, immune-mediated skin inflammatory disease that depending on the degree and type may affect the skin, nails, mucous membranes and joints, and may be potentially associated with systemic inflammation. The treatment of psoriasis is performed in order to obtain prolonged periods of remission of the disease and improvement of the quality of life of the patient. Pharmacological therapy consists of the use of vitamin D3 analogues and retinoids in combination with corticosteroids, and in the most severe cases immunosuppressive and chemotherapeutic agents, combined with topical therapy and phototherapy, are recommended. Although most established regimens are reasonably effective as short-term therapy, because of the safety profile of these drugs, their use for a short-term is limited, which makes it difficult to control the disease. Efforts are being made in the development of nanoparticles for dermatological applications, in order to provide sustained release of drugs, reduce toxicity and increase patient compliance to treatment. Triptolide, a diterpene with a triepoxide group, has anti-inflammatory, immunosuppressive, anti-cystogenesis and anti-tumor activity. Currently, the use of nanocarreadores demonstrated promising results for topical use and reduction of toxicity inherent to the molecule. Gene therapy by gene silencing using siRNAs is a new therapeutic modality, and its topical delivery can strategically modulate the expression of genes responsible for a variety of disorders, and several potential applications for siRNA therapy for skin diseases have already been studied. In this context, the present project aims at the development of a multifunctional liquid-crystalline phase dispersion that associates TNF-± siRNA with the drug triptolide. The nanodispersion will be analyzed for particle size and polydispersity index, zeta potential, differential scanning calorimetry, particle tracking, atomic force microscopy, polarized light microscopy and x-ray diffraction, physical particle stability, complexation efficiency / decomposition of siRNA into the system, drug encapsulation efficiency, and in vitro release assays using synthetic membrane and skin permeation / retention of swine ears using Franz diffusion cells. The cellular uptake ability of the siRNA-nanodispersion complex in cell culture of fibroblasts will also be evaluated through the cell viability studies by resazurin method, cellular uptake by confocal microscopy and flow cytometry and evaluation of the efficacy of silencing in the in vitro model of inflammation. The experimental strategy suggested in this project will result in a technological and therapeutic feasibility study of multifunctional liquid crystals for topical psoriasis therapy.
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