Tuning with Phosphorylcholine Grafts Improves the Physicochemical Properties of PLL/pDNA Nanoparticles at Neutral pH
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The improvement of biological properties of polycations is a fundamental step to overcome their limitations as non-viral gene carriers. This work studied the effect of phosphorylcholine (PC) groups on the physicochemical properties of poly(L-lysine) (PLL)/pDNA nanoparticles. Phosphorylcholine-grafted PLL derivatives (PLL-PC) containing increasing proportions of PC were obtained by the reductive amination reaction with phosphoryl glyceraldehyde and characterized by 1H NMR, FTIR, and GPC measurements. The PLL-PC derivatives were used to prepare polyplexes with pDNA and their properties were evaluated by fluorescence, gel electrophoresis and dynamic light scattering (DLS) measurements. The PLL-PC derivatives were able to interact with pDNA at low N/P ratios in physiological pH to form stable polyplexes having lower zeta potentials, as evidenced by the gel electrophoresis and zeta potentials measurements. A degree of grafting of 10% increased the in vitro transfection efficiency of PLL and a degree of 20 mol% of PC groups provided colloidal stability in physiological saline solution at neutral pH. Overall, the PC-PLL derivatives exhibited improved physicochemical properties and have significant potential for further studies as non-viral gene transfer agents. [Figure not available: see fulltext.].