(732d) Cationic Polylactides for siRNA Delivery

Cationic polymers have been broadly studied as scaffolds for gene delivery.  However, because typical cationic polymers cannot degrade readily, their long-term cytotoxicity is a serious concern.  Therefore, we are interested in integrating significant degradability with cationic polymers to create novel and safe polymeric materials for applications in gene delivery.  In this presentation, synthesis and characterization of cationic polylactides (CPLAs), as well as their application in siRNA delivery, will be described.  A series of CPLAs with different amounts of pendent tertiary amine functionalities were synthesized by the preparation of allyl-functionalized PLA via ring-opening polymerization, followed by thiol-ene click functionalization.  The CPLAs had well-controlled molecular weights and amine mol%, as well as low polydispersities.  With significant hydrolytic degradability, the CPLAs exhibited very low cytotoxicity via MTS cell viability assay, indicating that they are relatively safe materials for biomedical applications.  According to DLS and TEM analysis, CPLAs can readily complex with negatively charged siRNA to form CPLA-siRNA nanoplexes by electrostatic interaction.  In vitro studies showed that, with ready cell uptake of the CPLA-siRNA nanoplexes, efficient siRNA transfection via the nanoplexes can be realized.