Small Library of Prednisolone and Budesonide Conjugated Low and High Molecular Weight Polyethylenimine for Delivery of Plasmid DNA

In this study, a small library of prednisolone and budesonide conjugated polyethylenimine (PEI) derivatives was prepared. Since nuclear entry is a major barrier for plasmid DNA (pDNA) delivery, it is hypothesized that glucocorticoid-conjugated PEIs that employ their specific receptors to enter the cell nucleus may increase the gene transfer ability of PEI. In this study, prednisolone and budesonide were conjugated onto low and high molecular weight PEI (1.8 and 25 kDa) with different degrees of substitution via different linkers. The glucocorticoid-polyethyleneimine (GC–PEI)/pDNA polyplexes were prepared, and their biophysical characteristics, plasmid delivery, and cell-induced toxicity were evaluated. The polyplexes demonstrated a substantial ability to condense plasmid DNA and the protection of nucleic acids against enzymatic degradation. The polyplexes’ size was in the range of 50–250 nm with zeta potentials between 10 and 30 mV. Interestingly, prednisolone-conjugated low molecular weight PEI could enhance the level of desired protein expression by up to 4 folds with no toxicity compared to the parent unmodified polymer. The results of this study show a promising approach to preparing gene carrier vehicles based on low molecular weight PEI with low toxicity.