Branched poly(ethylenimine) (bPEI) is a well-studied cationic vector which exhibits superior gene transfection efficacies in a variety of cell lines. However, the high toxicity of PEI is a major concern for its use in clinical applications. The modifications of bPEI with various non-ionic, non-toxic moieties such as carbohydrates have been reported, in an effort to reduce its toxicity. In addition, the formulation of ternary complexes of PEI with anionic polymers is found to decrease its toxicity. The pH-responsive behavior of anionic polymers have been employed by others for drug delivery applications. In this report, pH-responsive statistical glycopolymers of linear and hyperbranched architectures are prepared via reversible addition-fragmentation chain transfer polymerization (RAFT) and are studied for their gene delivery applications. The anionic glycopolymers produced are studied for their toxicities, and membrane disruption properties, as a function of polymer architecture. Furthermore, the interactions of these anionic glycopolymers with Hep G2 and HEK 293T cells were studied as a function of time. These anionic glycopolymers were then complexed with bPEI at varying weight by weight (w/w) ratios to reduce the toxicity of PEI in vitro. The cellular uptake and gene expression of PEI polyplexes in the presence of anionic glycopolymers was directly related to the interactions of anionic glycopolymers with Hep G2 and HEK 293T cells.

Transfection efficiencies of PEI-anionic glycopolymer systems

246th National Meeting (2013)

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