Safety profile of dextran-spermine gene delivery vector in mouse lungs

• Main Authors: Yeo, Wendy Wai Yeng, Hosseinkhani, Hossein, Abdul Rahman, Sabariah, Rosli, Rozita, Domb, Abraham J., Abdullah, Syahrilnizam
• Format: Article
• Language: English
• Published: American Scientific Publishers 2014
• Online Access: http://psasir.upm.edu.my/id/eprint/29784/1/Safety%20profile%20of%20dextran%20spermine%20gene%20delivery%20vector%20in%20mouse%20lungs.pdf; http://psasir.upm.edu.my/id/eprint/29784/

A nano-sized polymer, dextran-spermine (D-SPM), was shown to have the capacity to deliver gene to the lung of mouse via intranasal route. In this study, assessments on the safety profile of D-SPM were performed to complement the gene expression results. African green monkey kidney fibroblast (COS-7) and human adenocarcinoma breast (MCF-7) cells transfected with D-SPM/pDNA showed massive reduction in the number of viable cells. As for in vivo study, elevated level of neutrophils was observed, despite the minimal level of pro-inflammatory cytokines (TNF-α, IL-12, IFN-γ detected in the bronchoalveolar lavage fluid (BALF) of mice treated with the D-SPM/pDNA complexes. Histology profile examinations of the lungs showed mild inflammatory responses, with inflamed areas overlap with healthy areas. Although reduction of mice weight was seen at day 1 post administration, the mice did not show any sign of abnormal behavior or physical appearance. Biodistribution study was performed to determine the ability of the D-SPM/pDNA complexes to infiltrate to other non-intended organs. The result showed that the D-SPM/pDNA complexes were only localized at the lung and no gene expression was detected in other organs or blood. In short, these results indicate that the D-SPM/pDNA exhibited mild toxicity in the mouse lungs.