Topical Administration of Dual siRNAs Using Fusogenic Lipid Nanoparticles for Treating Psoriatic-Like Plaques

Abstract

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.

Doxorubicin liposomes as an investigative model to study the skin permeation of nanocarriers

“…1,1-Di-(( Z )-octadec-9-en-1-yl)pyrrolidin-1-ium chloride (Cy5 lipid) was synthesized as reported (Marepally et al, 2014). 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl- sn -glycero-3-phosphoethanolamine (DOPE), 1,2-dioleoyl-3-trimethylammonium-propane (chloride salt) (DOTAP), 1,2-dioleoyl- sn -glycero-3-phosphate (DOPA), 1,2-distearoyl- sn -glycero-3-phosphoethanolamine-N-[amino(polyethyleneglycol)-2000] (ammonium salt) (DSPE-PEG 2000), 1,2-dioleoyl-sn-glycero-3-[(N-(5-amino-1-carboxypentyl) imidodiacetic acid) succinyl nickel salt] (DOGS-NTA-Ni) and cholesterol were purchased from Avanti Polar lipids (Alabaster, AL, USA).…”

Nucleic acid delivery into skin for the treatment of skin disease: Proofs-of-concept, potential impact, and remaining challenges

“…Similar to Hurley disease, TNFα is perhaps the most established drug target for treating severe forms of psoriasis [64]. Topical delivery of anti-TNFα siRNA as well as a siRNA cocktail including anti-TNFα and anti-STAT3 was shown to be effective at alleviating psoriasis-like symptoms in mice [33, 83]. Activated T helper cells have also been shown to play a major role in the manifestation of psoriasis, and selective skewing from Th1 phenotype to the IL-4 producing Th2 phenotype can alleviate psoriasis symptoms [84].…”

TNF-α in the cardiovascular system: from physiology to therapy

“…206 Furthermore, several reports from the field of targeted drug delivery and nanomedicine appear to open promising possibilities for local or tissue-targeted TNF-α gene silencing. Two different topical delivery systems (cationic amphiphilic lipid particles 207 and capsaicin-loaded cationic lipid-polymer hybrid nanoparticles) 208 have recently demonstrated efficacy in local transport of anti-TNF-α small interfering (si)RNA and in the treatment of experimental psoriasis. Moreover, the problem of insufficient endothelial siRNA transfection efficiency in vivo has recently been overcome by Dahlman et al,209 who developed a polymeric nanoconstruct (7C1) capable of delivering siRNAs specifically to endothelial cells, which allowed concurrent silencing of multiple endothelial genes.…”