title: Topical administration of dual siRNAs using fusogenic lipid nanoparticles for treating psoriatic-like plaques.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: College of Pharmacy & Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
authors.forename: Srujan
authors.initials: S
authors.lastname: Marepally
authors.forename: Cedar H A
authors.initials: CH
authors.lastname: Boakye
authors.forename: Apurva R
authors.initials: AR
authors.lastname: Patel
authors.forename: Chandraiah
authors.initials: C
authors.lastname: Godugu
authors.forename: Ravi
authors.initials: R
authors.lastname: Doddapaneni
authors.forename: Pinaki R
authors.initials: PR
authors.lastname: Desai
authors.forename: Mandip
authors.initials: M
authors.lastname: Singh
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002152:Calorimetry, Differential Scanning; D057809:HEK293 Cells; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D011565:Psoriasis / Q000188:drug therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D008055:Lipids; D034741:RNA, Small Interfering
keywords: Lipofectamine™ RNAiMAX; Psoriasis Area and Severity Index; dual-fusogenic-nucleic acid lipid particles; fusogenic-nucleic acid lipid particles; imiquimod; inflammation; psoriasis; siSTAT3; siTNF-α; stratum corneum plus epidermis