DNA delivery from photocrosslinked PEG hydrogels: encapsulation efficiency, release profiles, and DNA quality

Sustained DNA delivery from polymer matrices provides a means for enhanced and prolonged gene therapy; however, limitations exist with respect to tailoring the DNA release profiles and maintaining the quality of the encapsulated DNA over time. To address these issues, PEG-based macromolecular monomers were photopolymerized to produce hydrogels with various degradation rates to control the DNA release profiles. Photocrosslinked PEG-based hydrogels were designed that released DNA for periods of 6-100 days with either nearly linear or delayed burst release profiles. Plasmid DNA was released primarily in the relaxed and supercoiled forms, and the released DNA showed high biological activity in plated cell cultures. The addition of both chemical and physical protective agents helped preserve the supercoiled form of the plasmid DNA during photoencapsulation (up to 75% compared to non-encapsulated plasmid controls), thereby enhancing the biological activity of the released DNA.