Nanoparticulate DNA Packaging Using Terpolymers of Poly(lysine-g-(lactide-b-ethylene glycol))

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Abstract
Terpolymers of poly(lysine-g-(lactide-b-ethylene glycol)) (pK−pLL−pEG) were synthesized by using ring-opening polymerization and functional end-group grafting. Synthesis was characterized with gel permeation chromatography, proton nuclear magnetic resonance spectroscopy, and a trinitrobenzene sulfonic acid binding assay. Polymer association behavior with DNA was investigated using an ethidium bromide exclusion assay, static light scattering, and scanning electron microscopy. Polylactide molecular weight was varied to investigate its impact on DNA association and resulting complex characteristics. Polylysine ( = 8800, DP = 42) modified with either 7400 or 10 870 pLL−pEG reduced the minimum amount of primary amines necessary for complete condensation by 23% and 48%, respectively, compared to unmodified polylysine (pK42). Complexes formed with the highest molecular weight terpolymer demonstrated significantly (p < 0.1) greater resistance to DNase I than lyophilized pK42−DNA particles. This study suggests that modification of pK42 with pLL−pEG diblock copolymers impacts polylysine's associative and binding behavior to DNA and resulting particle characteristics. Modulation of terpolymer composition in complexes can enable control over intracellular plasmid dissociation rates to improve transfection efficiency.