Screening of siRNA nanoparticles for delivery to airway epithelial cells using high-content analysis. (August 2011)

• Record Type: Journal Article
• Authors: Hibbitts, Alan; Lieggi, Nora; McCabe, Olive; Thomas, Warren; Barlow, James; O''Brien, Fiona; Cryan, Sally-Ann
• Is Part Of: Therapeutic delivery. Volume 2:Number 8(2011)
• Page Start: 987
• Page End: 999
• Publication Date: 2011-08
• Subjects: Drug delivery systems -- Periodicals; Therapeutics -- Periodicals; 615.6
• DOI: 10.4155/tde.11.73
• Languages: English
• ISSNs: 2041-5990

Abstract

Aims: Delivery of siRNA to the lungs via inhalation offers a unique opportunity to develop a new treatment paradigm for a range of respiratory conditions. However, progress has been greatly hindered by safety and delivery issues. This study developed a high-throughput method for screening novel nanotechnologies for pulmonary siRNA delivery.Methodology: Following physicochemical analysis, the ability of PEI–PEG–siRNA nanoparticles to facilitate siRNA delivery was determined using high-content analysis (HCA) in Calu-3 cells. Results obtained from HCA were validated using confocal microscopy. Finally, cytotoxicity of the PEI–PEG–siRNA particles was analyzed by HCA using the Cellomics ® multiparameter cytotoxicity assay.Conclusion: PEI–PEG–siRNA nanoparticles facilitated increased siRNA uptake and luciferase knockdown in Calu-3 cells compared with PEI–siRNA.