Balancing gene transfection and cytotoxicity of nucleic acid carriers with focus on ocular and hepatic disorders: evaluation of hydrophobic and hydrophilic polyethyleneimine derivatives
Fernando A. de Oliveira, Lindomar J. C. Albuquerque, Michelle Nascimento-Sales, Marcelo A. Christoffolete, Ismael C. Bellettini, Fernando C. Giacomelli
Abstract
) nevertheless, results in higher levels of cytotoxicity and respective lower transfection rates. The sugar-decorated polyplexes are overall less cytotoxic, but the presence of lactose moieties also leads to larger polyplexes and notably weak polymer-DNA binding, which compromise the transfection efficiency. Yet, along with the presence of short lytic alkyl domains, the double-substitution of PEI synergistically boosts gene transfection probably due to the uptake of higher DNA and polymer amounts without cell damage. Overall, the experimental data suggest that ocular and hepatic gene therapies may be potentialized by fine-tuning the hydrophobic-to-hydrophilic balance, and succinic acid is a favorable motif for the modification of PEI.