Synthesis of Water-Soluble Imidazolium Polyesters as Potential Nonviral Gene Delivery Vehicles

The inherent hydrolytic reactivity of polyesters renders them excellent candidates for a variety of biomedical applications. Incorporating ionic groups further expands their potential impact, encompassing charge-dependent function such as deoxyribonucleic acid (DNA) binding, antibacterial properties, and pH-responsiveness. Catalyst-free and solvent-free polycondensation of a bromomethyl imidazolium-containing (BrMeIm) diol with neopentylglycol (NPG) and adipic acid (AA) afforded novel charged copolyesters with pendant imidazolium sites. Varying ionic content influenced thermal properties and offered a wide-range, -41 to 40 degrees C, of composition-dependent glass transition temperatures (T(g)s). In addition to desirable melt and thermal stability, polyesters with ionic concentrations >= 15 mol % readily dispersed in water, suggesting potential as nonviral gene delivery vectors. An electrophoretic gel shift assay confirmed the novel cationic copolyesters successfully bound DNA at an N/P ratio of 4 for 50 mol % and 75 mol % charged copolyesters (P(NA(50)-co-ImA(50)) and P(NA(25)-co-ImA(75))), and an N/P ratio of 5 for 100 mol % Im (PImA). Polyplexes exhibited insignificant cytotoxicity even at high concentrations (200 mu g/mL), and a Luciferase transfection assay revealed the ionic (co)polyesters transfected DNA significantly better than the untreated controls. The successful transfection of these novel (co)polyesters inspires future imidazolium-containing polyester design.