Treatment of psoriasis with NFKBIZ siRNA using topical ionic liquid formulations

Area of Science:

• Dermatology
• Molecular Biology
• Biotechnology

Background:

• Systemic anti-tumor necrosis factor-α (TNF-α) and anti-interleukin-17A (IL-17A) antibodies are effective for plaque psoriasis but raise safety concerns.
• Targeting upstream molecules like NFKBIZ locally could offer an alternative therapeutic strategy.
• Effective topical delivery of small interfering RNA (siRNA) to the skin remains a significant challenge due to the skin's barrier properties and siRNA instability.

Purpose of the Study:

• To investigate the potential of ionic liquids for topical delivery of NFKBIZ siRNA.
• To evaluate the therapeutic efficacy of locally delivered NFKBIZ siRNA in a psoriasis model.

Main Methods:

• Development of an ionic liquid formulation for enhanced skin penetration of NFKBIZ siRNA.
• Application of the siRNA formulation to a psoriasis model.
• Assessment of gene expression changes and downstream signaling pathways, including TNF-α and IL-17A.

Main Results:

• Successful topical delivery of NFKBIZ siRNA into the skin was achieved using ionic liquids.
• Treatment with NFKBIZ siRNA suppressed aberrant gene expression characteristic of psoriasis.
• Down-regulation of key psoriasis-related inflammatory signals, including TNF-α and IL-17A, was observed.

Conclusions:

• Ionic liquids provide an effective platform for topical siRNA delivery to the skin.
• Local silencing of NFKBIZ via topical siRNA demonstrates therapeutic potential for psoriasis treatment.
• This approach offers a promising alternative to systemic biologics, potentially mitigating safety concerns.