Synthesis of polyethylene glycol-oligo (glutamic acid) conjugated with polyethylenimine-dexamethasone for gene delivery applications.

ABSTRACT

In this study, polyethylenimine-dexamethasone (PEI-Dexa) was conjugated to polyethylene glycol-oligo (glutamic acid) derivatives (PEG-Glu), and the ability of this conjugated derivative's gene transfection efficiency was investigated. Dexamethasone is the potent ligand of the glucocorticoid receptor which facilitates the transfer into nucleus, and it is known to enlarge the nuclear pore complexes. PEG facilitates the formation of polyplexes with improved solubility, reduced aggregation, lower cytotoxicity, and possibly decreases opsonization with serum proteins in the bloodstream. In gel retardation assays, PEG-Glu8-PEI-Dexa/pDNA and PEG-Glu10-PEI-Dexa/pDNA were completely retarded at or above polymer pDNA weight ratios of 14 and 12, respectively. The physicochemical characteristics were studied by measuring the average size distribution and zeta-potential values of the complexes. In vitro transfection assays showed that PEG-Glu-PEI-Dexa/pDNA complexes displayed higher gene delivery efficiency than the PEI 2 kDa/pDNA complexes. In addition, PEG-Glu-PEI-Dexa was less toxic than PEI 25 kDa. These results indicate that PEG-Glu-PEI-Dexa has the potential to be used as an efficient gene carrier for nonviral gene therapy.