期刊
NANOMEDICINE
卷 9, 期 14, 页码 2157-2174出版社
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.13.202
关键词
dual-fusogenic-nucleic acid lipid particles; fusogenic-nucleic acid lipid particles; imiquimod; inflammation; Lipofectamine (TM) RNAiMAX; psoriasis; Psoriasis Area and Severity Index; siSTAT3; siTNF-alpha; stratum corneum plus epidermis
资金
- National Center for Research Resources
- National Institute of Minority Health and Health Disparities of the NIH [8 G12 MD007582-28, 2 G12 RR003020]
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.
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