(109b) Well-Defined Cationic Polylactides As Biodegradable Vector for Effective Delivery of Plasmid DNA

Two well-defined cationic polylactides (CPLAs) with different densities of pendant tertiary amine functionalities were synthesized by thiol-ene click functionalization of an allyl-functionalized polylactide. Well-defined chemical structures of CPLAs were characterized by ¹H-NMR and GPC. Additionally, the degradability of CPLAs at aqueous condtions was systematically studied using GPC as a analytic tool. Having significant hydrolytic degradability, CPLAs were utilized to complex with plasmid DNA (pDNA) to yield CPLA/pDNA polyplexes through electrostatic interaction. Biophysical properties of such polyplexes including size, surface potential and morphology were characterized by DLS and TEM. pDNA encoding luciferase was delivered to two physiological distinct cell lines (macrophage and fibroblast) via these polyplexes. The formulated polyplexes led to high levels of transfection while exhibiting low toxicity. Gene transfection efficiency was positively correlated with charge density of CPLAs, as well as polymer:pDNA weight ratios in the polyplexes. Results of this work provide helpful guidelines for the design of next-generation biodegradable biomaterials for gene delivery applications.