Temperature- and pH-sensitive hydrogels to immobilize heparin-modified PEI/DNA complexes for sustained gene delivery

Temperature- and pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid-co-poly(ε-caprolactone)) (P(NIPAAm-co-AAc-co-PCL)) hydrogels were synthesized to immobilize plasmid DNA (pDNA) compacted with heparin-modified polyethyleneimine (Hep/PEI). The interior morphology of the prepared hydrogels observed by SEM showed macroporous structure clearly. It was found that the swollen hydrogels with low PCL content were able to immobilize efficiently plasmid DNA complexes. The de-swollen hydrogels resulted in a sustained release of the immobilized DNA complexes, and the released DNA complexes exhibited considerable gene expression activity with reduced cytotoxicity as compared with DNA complexes in the solution, indicating that the heparin-modified PEI/DNA-complex-immobilized environment-sensitive hydrogel has promising applications in substrate-mediated gene delivery.