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  • Title: Dendrimer/DNA complexes encapsulated functional biodegradable polymer for substrate-mediated gene delivery.
    Author: Fu HL, Cheng SX, Zhang XZ, Zhuo RX.
    Journal: J Gene Med; 2008 Dec; 10(12):1334-42. PubMed ID: 18816481.
    Abstract:
    BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The fast degrading functional polymer has great potential for localized transfection.
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