Synthesis and characterization of polyethyleneimine-terminated poly(β-amino esters) conjugated with pullulan for gene delivery

Cationic polymers endowed with a flexible system for condensing DNA, are regarded as effective materials for gene delivery. The synthesis of poly(β-amino esters) (pBAEs) based on 1,4-butanediol diacrylate-ethanolamine monomer (1.2:1 molar ratio) and 1,4-butanediol diacrylate-ethylene diamine (1:2 molar ratio) was carried out and modification with 1800 Da polyethyleneimine (PEI) at different weight ratios (3 and 1) as well as conjugation with pullulan in various weight ratios of (0.0625, 0.125, 0.25, and 1) was performed. Gel-retardation assay demonstrated that the synthesized polymers were able to condense DNA at low carrier/plasmid (C/P) ratios. The polyplexes with ratio 3 of PEI (pβ 1 /PEI 3 ) were restricted in all C/P ratios and the polyplexes of pβ 1 /PEI 3 /pull 0.125 were condensed at C/P ratios higher than 0.5. The particle size at C/P was approximately about 200 nm with a positive surface charge. The presence of the pullulan in the structure of the synthesized pBAEs could be effective in reducing toxicity of the base polymer. Highest metabolic activity was dedicated to C/P 2 of pβ 2 /PEI 3 /pull 0.125 with 80.6% viability. Furthermore, the most efficient gene reporter delivery was seen at C/P ratio of 6 in pβ 2 /PEI 3 /pull 0.125 nanoparticles. Therefore, pullulan grafting could enhance the cellular response of cells in terms of cytotoxicity and transfection efficiency.