Research

Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor

Xiaoqin Wang^1,2 , Weidong Xu² , Subhra Mohapatra^3,4 , Xiaoyuan Kong² , Xu Li¹ , Richard F Lockey^2,4 and Shyam S Mohapatra^2,4

¹Clinical Laboratory Center of First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, China

²Division of Allergy and Immunology, Culverhouse Airway Disease and Nanomedicine Research Center, University of South Florida College of Medicine, Tampa, Florida, USA

³Endocrinology Division, Internal Medicine, University of South Florida College of Medicine, Tampa, Florida, USA

⁴James A. Haley VA Medical Center, Tampa, Florida, USA

author email corresponding author email

Genetic Vaccines and Therapy 2008, 6:7doi:10.1186/1479-0556-6-7

Published:	15 February 2008

Abstract

Background

Asthma is a complex disease, characterized by reversible airway obstruction, hyperresponsiveness and chronic inflammation. Principle pharmacologic treatments for asthma include bronchodilating beta2-agonists and anti-inflammatory glucocorticosteroids; but these agents do not target the main cause of the disease, the generation of pathogenic Th2 cells. We previously reported reduction in allergic inflammation in mice deficient in the ANP receptor NPRA. Here we determined whether siRNA for natriuretic peptide receptor A (siNPRA) protected against asthma when administered transdermally.

Methods

Imiquimod cream mixed with chitosan nanoparticles containing either siRNA green indicator (siGLO) or siNPRA was applied to the skin of mice. Delivery of siGLO was confirmed by fluorescence microscopy. The anti-inflammatory activity of transdermal siNPRA was tested in OVA-sensitized mice by measuring airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines.

Results

SiGLO appearing in the lung proved the feasibility of transdermal delivery. In a mouse asthma model, BALB/c mice treated with imiquimod cream containing siNPRA chitosan nanoparticles showed significantly reduced airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines IL-4 and IL-5 in lung homogenates compared to controls.

Conclusion

These results demonstrate that topical cream containing imiquimod and siNPRA nanoparticles exerts an anti-inflammatory effect and may provide a new and simple therapy for asthma.