Topical administration of dual siRNAs using fusogenic lipid nanoparticles for treating psoriatic-like plaques. (2014)

• Record Type: Journal Article
• Authors: Marepally, Srujan; Boakye, Cedar HA; Patel, Apurva R; Godugu, Chandraiah; Doddapaneni, Ravi; Desai, Pinaki R; Singh, Mandip
• Is Part Of: Nanomedicine. Volume 9:Number 14(2014)
• Page Start: 2157
• Page End: 2174
• Publication Date: 2014
• Subjects: dual-fusogenic-nucleic acid lipid particles -- fusogenic-nucleic acid lipid particles -- imiquimod -- inflammation -- Lipofectamine™ RNAiMAX -- psoriasis -- Psoriasis Area and Severity Index -- siSTAT3 -- siTNF-α -- stratum corneum plus epidermis; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.13.202
• Languages: English
• ISSNs: 1743-5889

Abstract

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-α siRNA (siTNF-α). 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 µm. F-NALPs carrying siSTAT3 and siTNF-α significantly (p < 0.05) reduced expression of STAT3 and TNF-α mRNAs and IL-23 and Ki-67 proteins compared with solution, and was superior in comparison with Topgraf ® (GlaxoSmithKline Pharmaceuticals Limited, Maharashtra, India).Conclusion: Our observations demonstrate that F-NALPs can efficiently carry siSTAT3 and siTNF-α into the dermis and combination of the two nucleic acids can synergistically treat psoriatic-like plaques. Original submitted 5 June 2013; Revised submitted 14 October 2013