Safety Profile of Dextran-Spermine Gene Delivery Vector in Mouse Lungs

Abstract

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 nonintended 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.

Water soluble cationic dextran derivatives containing poly(amidoamine) dendrons for efficient gene delivery

“…Up to now, some cationic dextran derivatives have been synthesized and investigated for gene delivery. For example, Li et al (2013) prepared dextrangraft-poly((2-dimethyl amino)ethyl methacrylate) as an efficient delivery system for tumor gene therapy; Thomas, Rekha, and Sharma (2010) prepared cationic dextran-protamine conjugate as a haemocompatible and nonviral gene vector; Yeo et al (2014) conjugated spermine onto dextran for delivering gene to the lung of mouse via intranasal route. However, the efficiency of gene delivery by these cationic dextran derivatives is still relatively low when compared to commonly used polyethylenimine (PEI) or cationic lipids.…”

Polysaccharide-Based Conjugates for Biomedical Applications

“…133 Oxidized dextran spermine conjugate nano particle system successfully delivered genetic materials. [134][135][136] such as: pCMV-GFP plasmid, 137 pSV-LacZ. 138,139 Dextran-spermine and lipoplexes were compared.…”

Cationic Polymers for the Delivery of Therapeutic Nucleotides

“…PEG/oleate residues are, therefore, attached to polymers, which results in better transfection efficiency in serum-rich medium (Azzam et al 2004). Dextran-spermine for the delivery of pDNA to mouse lungs by intranasal route exhibits mild toxicity (Yeo et al 2014). Polyelectrolyte complexes (PECs) with dextran sulfate have also been developed to minimize interaction with blood components.…”