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Published on: April 16, 2019
Topical administration of dual siRNAs using fusogenic lipid nanoparticles for treating psoriatic-like plaques
Srujan Marepally1, Cedar H A Boakye, Apurva R Patel
1College of Pharmacy & Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
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.
