Topical administration of dual siRNAs using fusogenic lipid nanoparticles for treating psoriatic-like plaques

Aim: Psoriasis is a chronic autoimmune skin disorder with substantial negative impact on the patient's quality of life. The present study was carried out to demonstrate the efficiency of a novel topical delivery system in the transport of two siRNAs for the treatment of psoriatic-like plaques. Materials & methods: We designed and developed a novel fusogenic nucleic acid lipid particle (F-NALP) system containing two therapeutic nucleic acids, anti-STAT3 siRNA (siSTAT3) and anti-TNF-alpha siRNA (siTNF-alpha). Novel cationic amphiphilic lipid with oleyl chains was synthesized and used in the nanocarrier system. Therapeutic efficacies of F-NALPs were assessed using an imiquimod-induced psoriatic-like plaque model. Results: Hydrodynamic size and surface potential of F-NALPs were 102 +/- 6 nm and 32.14 +/- 6.21 mV, respectively. F-NALPs delivered fluorescein isothiocyanate-siRNA to a skin depth of 360 mu m. F-NALPs carrying siSTAT3 and siTNF-alpha significantly (p < 0.05) reduced expression of STAT3 and TNF-alpha mRNAs and IL-23 and Ki-67 proteins compared with solution, and was superior in comparison with Topgraf (R) (GlaxoSmithKline Pharmaceuticals Limited, Maharashtra, India). Conclusion: Our observations demonstrate that F-NALPs can efficiently carry siSTAT3 and siTNF-alpha into the dermis and combination of the two nucleic acids can synergistically treat psoriatic-like plaques.