Dendrimer/DNA complexes encapsulated functional biodegradable polymer for substrate‐mediated gene delivery

Abstract

To overcome the extracellular barriers in gene delivery and direct gene delivery to target tissues, substrate-mediated transfection, which sustains the release of naked DNA or vector/DNA complexes, and also supports cell growth, has been developed. In the present study, polyamidoamine (PAMAM) dendrimer/DNA complexes encapsulated functional biodegradable polymer films for substrate-mediated gene delivery were prepared. To maintain the activity of DNA during dehydration, the dendrimer/DNA complexes were encapsulated in a water soluble polymer, poly alpha,beta-[N-(2-hydroxyethyl)-(L)-aspartamide], and then deposited on or sandwiched in functional polymer films with a fast degradation rate to mediate gene transfection. The in vitro gene transfections of pGL3-Luc and pEGFP-C1 plasmids in HEK293 cells mediated by different films were studied. For comparison, the transfection mediated by the film fabricated by conventional linear poly((DL)-lactide) was also investigated. The expression of pGL3-Luc and pEGFP-C1 plasmids could effectively be mediated by the PAMAM/DNA complexes deposited or sandwiched polymer films, with transfection efficiencies comparable to that of solution-based transfections. The cells on the functionalized star poly((DL)-lactide) film exhibited much higher gene expression compared to the cells on the conventional linear poly((DL)-lactide) film because the fast degradation rate of star poly((DL)-lactide) facilitated the access of PAMAM/DNA complexes for the cells seeded on the film. In addition, the films did not exhibit any additional cytotoxicity to the cells during the degradation and transfection. The fast degrading functional polymer has great potential for localized transfection.